Signal Transduction Cascades

Size: px
Start display at page:

Download "Signal Transduction Cascades"

Transcription

1 Signal Transduction Cascades

2 Contents of this page: Kinases & phosphatases Protein Kinase A (camp-dependent protein kinase) G-protein signal cascade Structure of G-proteins Small GTP-binding proteins, GAPs & GEFs Phosphatidylinositol signal cascades

3 Kinases and Phosphatases: Many enzymes are regulated by covalent attachment of phosphate, in ester linkage, to the side-chain hydroxyl group of a particular amino acid residue (serine, threonine or tyrosine).

4 A protein kinase transfers the terminal phosphate of ATP to a hydroxyl group on a protein. A protein phosphatase catalyzes removal of the phosphate by hydrolysis.

5 Phosphorylation may directly alter activity of an enzyme, e.g., by promoting a conformational change. Alternatively, altered activity may result from binding another protein that specifically recognizes a phosphorylated domain. For example, proteins bind to domains that include phosphorylated serine or threonine in the sequence RXXX[pS/pT]XP, where X can be different amino acids. Binding to is a mechanism by which some proteins (e.g., transcription factors) may be retained in the cytosol, and prevented from entering the cell nucleus.

6 Protein kinases and phosphatases are themselves regulated by complex signal cascades. For example: Some protein kinases are activated by Ca++-calmodulin. Protein Kinase A is activated by cyclic- AMP (camp).

7 As discussed earlier, Adenylate Cyclase (Adenylyl Cyclase) catalyzes: ATP camp + PPi Binding of certain hormones (e.g., epinephrine) to the outer surface of a cell activates Adenylate Cyclase to form camp within the cell. Cyclic AMP is thus considered to be a second messenger. Phosphodiesterase enzymes catalyze: camp + H2O AMP The phosphodiesterase that cleaves camp is activated by phosphorylation catalyzed by Protein Kinase A. Thus camp stimulates its own degradation, leading to rapid turnoff of a camp signal.

8 Protein Kinase A (camp-dependent Protein Kinase) transfers Pi from ATP to the hydroxyl group of a serine or threonine that is part of a particular 5-amino acid sequence. Protein Kinase A exists in the resting state as a complex of: 2 regulatory subunits (R)( 2 catalytic subunits (C)

9 Each regulatory subunit (R) of Protein Kinase A contains a pseudosubstrate sequence comparable to the substrate domain of a target protein for Protein Kinase A, but with alanine substituting for the serine or threonine. The pseudosubstrate domain of the regulatory subunit, which lacks a hydroxyl that can be phosphorylated, binds to the active site of the catalytic subunit, blocking its activity.

10 When each regulatory subunit binds 2 camp, a conformational change causes the regulatory subunits to release the catalytic subunits. Each catalytic subunit (C) can then catalyze phosphorylation of serine or threonine residues on target proteins. R2C2 + 4 camp R2cAMP4 + 2 C

11 AKAPs,, A-Kinase anchoring proteins, bind to the regulatory subunits of Protein Kinase A. AKAPs localize Protein Kinase A to specific regions of a cell. PKIs,, Protein Kinase Inhibitors, modulate activity of the catalytic subunit

12 G Protein Signal Cascade A hormone (e.g., epinephrine or glucagon), that activates formation of cyclic AMP, binds at the cell surface to a receptor with seven transmembrane a-helices. Rhodopsin, depicted at right and below was the first member of the family of 7-helix receptors to have its structure determined by X-ray crystallography. 7-Helix receptors that interact with G- proteins are called GPCR, or G-Protein- Coupled Receptors.

13 Various proteins interact with GPCRs to modulate their activity. Effects of these interactions include altered ligand affinity, receptor dimerization that may enhance or alter activity, altered receptor localization, etc. Ligand-induced receptor clustering may also regulate receptor function. A G-protein that is part of a pathway that stimulates Adenylate Cyclase is called Gs, and its subunit G.

14 The subunit of a G-protein (G ) ) binds GTP, and can hydrolyze it to GDP + Pi. P The and subunits have covalently attached lipid anchors, that insert into the plasma membrane, binding a G-protein to the cytosolic surface of the plasma membrane. Adenylate Cyclase (AC) is a transmembrane protein, with cytosolic domains forming the catalytic site. The complex of & subunits, G inhibits G.

15 The sequence of events by which a hormone activates camp signaling is depicted in the diagram above and summarized below: 1. Initially the a subunit of G-protein has bound GDP, and the a, b, & g subunits are complexed together. 2. Hormone binding to a 7-helix receptor (GPCR) causes a conformational change in the receptor that is transmitted to the G- protein. The nucleotide-binding site on Ga G becomes more accessible to the cytosol, where [GTP] is usually higher than [GDP]. Ga G releases GDP and binds GTP. (GDP-GTP( exchange) 3. Substitution of GTP for GDP causes another conformational change in Ga. Ga-GTP dissociates from the inhibitory bg subunit complex, and can now bind to and activate Adenylate Cyclase. 4. Adenylate Cyclase,, activated by Ga-GTP, G catalyzes synthesis of camp. 5. Protein Kinase A (camp-dependent Protein Kinase) catalyzes phosphorylation of various cellular proteins, altering their activity.

16 Turn off of the signal: 1. Ga hydrolyzes GTP to GDP + Pi (GTPase). The presence of GDP on Ga causes it to rebind to the inhibitory bg complex. Adenylate cyclase is no longer activated. 2. Phosphodiesterase catalyzes hydrolysis of camp to AMP. 3. Hormone receptor desensitization occurs. This process varies with the hormone. Some receptors are phosphorylated via G- protein-coupled receptor kinases. The phosphorylated receptor may then bind to a protein arrestin that blocks receptor-g-protein activation and promotes removal of the receptor from the membrane by clathrin-mediated endocytosis. 4. Protein Phosphatase catalyzes removal by hydrolysis of phosphates that were attached to proteins via Protein Kinase A.

17 Signal amplification is an important feature of signal cascades. One hormone molecule can lead to formation of many camp molecules. Each catalytic subunit of Protein Kinase A catalyzes phosphorylation of many proteins during the life-time of the camp.

18 The stimulatory Gsa, G, when it binds GTP, activates Adenylate Cyclase. An inhibitory Gia,, when it binds GTP, inhibits Adenylate Cyclase. Different effectors and their receptors induce Gia toexchange GDP for GTP than those that activate Gsa. In some cells, the complex of G that is released when Ga G binds GTP is itself an effector that binds to and activates other proteins.

19 Cholera toxin catalyzes covalent modification of Gsa.. ADP-ribose is transferred from NAD+ to an arginine residue at the GTPase active site of Gsa. This ADP-ribosylation prevents Gsa from hydrolyzing GTP. Thus Gsa becomes permanently activated. Pertussis toxin (whooping cough disease) catalyzes ADP-ribosylation at a cysteine residue of Gia,, making the inhibitory Ga incapable of exchanging GDP for GTP. Thus the inhibitory pathway is blocked. ADP-ribosylation is a general mechanism by which activity of many proteins is regulated, in eukaryotes (including mammals) as well as in prokaryotes.

20 Structure of G proteins: The nucleotide binding site in Ga consists of loops that extend out from the edge of a 6-stranded b-sheet.. The a subunit of an inhibitory G-Protein, complexed with GTPgS, a non-hydrolyzable analog of GTP, is shown at right. Three switch domains have been identified, that change position when GTP substitutes for GDP on Ga.. These domains include residues adjacent to the terminal phosphate of GTP and/or the Mg++ associated with the two terminal phosphates

21 GTP hydrolysis occurs by nucleophilic attack of a water molecule on the terminal phosphate of GTP. Switch domain II of Ga G includes a conserved glutamine residue that helps to position the attacking water molecule adjacent to GTP at the active site.

22 The b subunit of the heterotrimeric G-protein has a b-propeller structure, formed from multiple repeats of a sequence called the WD-repeat.. The b- propeller provides a stable structural support for residues that bind Ga.

23 The family of heterotrimeric G-proteins includes also: the protein transducin,, involved in sensing of light in the retina. G-proteins involved in odorant sensing in olfactory neurons.

24 There is a larger family of small GTP- binding switch proteins,, related to Ga G, that will not be discussed here. They include (with roles indicated): initiation & elongation factors (protein synthesis) Ras (growth factor signal cascades) Rab (membrane vesicle targeting and fusion) ARF (formation of vesicle coatomer coats) Ran (transport of proteins into & out of the nucleus) Rho (regulation of actin cytoskeleton) All GTP-binding proteins differ in conformation depending on whether GDP or GTP is present at their nucleotide binding site. Generally GTP binding induces the active conformation.

25 Most GTP-binding proteins depend on helper proteins: GAPs, GTPase Activating Proteins, promote GTP hydrolysis. A GAP may provide an essential active site residue, while promoting the correct positioning of the glutamine residue of the switch II domain. Frequently a positively charged arginine residue of a GAP inserts into the active site and helps to stabilize the transition state by interacting with negatively charged oxygen atoms of the terminal phosphate of GTP during hydrolysis. Ga of a heterotrimeric G protein has innate capability for GTP hydrolysis. It has the essential arginine residue normally provided by a GAP for small GTPbinding proteins. However, RGS proteins, which are negative regulators of G protein signaling, stimulate GTP hydrolysis by Ga. GEFs, Guanine nucleotide Exchange Factors, promote GDP/GTP exchange. The activated receptor (GPCR) serves as GEF for a heterotrimeric G protein.

26 Phosphatidylinositol signal cascades: Some hormones activate a signal cascade based on the membrane lipid phosphatidylinositol, shown at right. The sequence of events follows :

27 1. Kinases catalyze sequential transfer of Pi from ATP to hydroxyl groups at positions 5 & 4 of the inositol ring of phosphatidylinositol, to yield phosphatidylinositol-4,5-bisphosphate (PIP2). 2. PIP2 is cleaved by Phospholipase C. Different isoforms of Phospholipase C have different regulatory domains, and thus respond to different signals. One form of Phospholipase C is activated by a G-protein designated Gq. A GPCR (receptor) is activated. GTP exchanges for GDP. Then Gqa- GTP activates Phospholipase C. C

28 Ca++,, which is required for activity of Phospholipase C, interacts with negatively charged residues and with phosphate moieties of IP3 at the active site. 3. Cleavage of PIP2 by Phospholipase C yields two second messengers, inositol- 1,4,5-trisphosphate (IP3), and diacylglycerol (DG( DG)

29 4. Diacylglycerol,, with Ca++,, activates Protein Kinase C,, which catalyzes phosphorylation of several cellular proteins, altering their activity.

30 5. IP3 (inositol-1,4,5-trisphosphate) activates Ca+ + release channels in endoplasmic reticulum (ER) membranes. Ca++ stored in the ER is released to the cytosol,, where it may bind to calmodulin, or may help to activate Protein Kinase C.

31 Signal turn-off includes removal of Ca++ from the cytosol by action of Ca++-ATPase pumps, and degradation of IP3. Sequential dephosphorylation of IP3 (inositol-1,4,5- trisphosphate) by enzyme-catalyzed hydrolysis yields inositol,, which is a substrate for synthesis of phosphatidylinositol.

32 IP3 may instead be phosphorylated via specific kinases, converting it to IP4, IP5 or IP6. Some of these have signal roles. For example, the IP4 inositol-1,3,4,5-tetraphosphate in some cells activates plasma membrane Ca++ channels.

33 The kinases that convert PI (phosphatidylinositol) to PIP2 (PI- 4,5-bisphosphate, see above) transfer phosphate from ATP to hydroxyls at positions 4 & 5 of the inositol ring. PI 3-Kinases instead catalyze phosphorylation of phosphatidylinositol at the 3 position of the inositol ring. For example, phosphatidylinositol-3- phosphate (PI-3-P) is shown at right. PI-3-P, PI-3,4-P2, PI-3,4,5-P3, and PI-4,5-P2 have signaling roles. These lipids are ligands for particular pleckstrin homology (PH) and FYVE protein domains that bind proteins to membrane surfaces.

34 Protein Kinase B (also called Akt) ) becomes activated when it is recruited from the cytosol to the plasma membrane surface by binding to products of PI-3 Kinase, such as PI-3,4,5-P3. Other kinases at the cytosolic surface of the plasma membrane then catalyze phosphorylation of Protein Kinase B, activating it.

35 The activated Protein Kinase B catalyzes phosphorylation of serine or threonine residues of many proteins, with diverse effects on metabolism, cell growth, and apoptosis. Downstream metabolic effects of Protein Kinase B activity include stimulation of glycogen synthesis, stimulation of glycolysis, and inhibition of gluconeogenesis.

36 Signal cascades may be mediated by complexes of proteins that assemble at the cytosolic surface of the plasma membrane, frequently in areas of distinct lipid composition called lipid rafts lipid rafts. Signal proteins may be recruited into such complexes by: insertion of their lipid anchors in the plasma membrane, interaction with membrane-associated scaffolding proteins,, or interaction of their pleckstrin homology domains with transiently formed phosphatidylinositol derivatives.

Signal Transduction: G-Protein Coupled Receptors

Signal Transduction: G-Protein Coupled Receptors Signal Transduction: G-Protein Coupled Receptors Federle, M. (2017). Lectures 4-5: Signal Transduction parts 1&2: nuclear receptors and GPCRs. Lecture presented at PHAR 423 Lecture in UIC College of Pharmacy,

More information

Cell Signaling part 2

Cell Signaling part 2 15 Cell Signaling part 2 Functions of Cell Surface Receptors Other cell surface receptors are directly linked to intracellular enzymes. The largest family of these is the receptor protein tyrosine kinases,

More information

Receptor mediated Signal Transduction

Receptor mediated Signal Transduction Receptor mediated Signal Transduction G-protein-linked receptors adenylyl cyclase camp PKA Organization of receptor protein-tyrosine kinases From G.M. Cooper, The Cell. A molecular approach, 2004, third

More information

Lipids and Membranes

Lipids and Membranes Lipids and Membranes Presented by Dr. Mohammad Saadeh The requirements for the Pharmaceutical Biochemistry I Philadelphia University Faculty of pharmacy Membrane transport D. Endocytosis and Exocytosis

More information

Enzymes Part III: regulation II. Dr. Mamoun Ahram Summer, 2017

Enzymes Part III: regulation II. Dr. Mamoun Ahram Summer, 2017 Enzymes Part III: regulation II Dr. Mamoun Ahram Summer, 2017 Advantage This is a major mechanism for rapid and transient regulation of enzyme activity. A most common mechanism is enzyme phosphorylation

More information

Propagation of the Signal

Propagation of the Signal OpenStax-CNX module: m44452 1 Propagation of the Signal OpenStax College This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution License 3.0 By the end of this section,

More information

Sarah Jaar Marah Al-Darawsheh

Sarah Jaar Marah Al-Darawsheh 22 Sarah Jaar Marah Al-Darawsheh Faisal Mohammad Receptors can be membrane proteins (for water-soluble hormones/ligands) or intracellular (found in the cytosol or nucleus and bind to DNA, for lipid-soluble

More information

Mechanisms of Hormone Action

Mechanisms of Hormone Action Mechanisms of Hormone Action General principles: 1. Signals act over different ranges. 2. Signals have different chemical natures. 3. The same signal can induce a different response in different cells.

More information

Signal Transduction Pathways. Part 2

Signal Transduction Pathways. Part 2 Signal Transduction Pathways Part 2 GPCRs G-protein coupled receptors > 700 GPCRs in humans Mediate responses to senses taste, smell, sight ~ 1000 GPCRs mediate sense of smell in mouse Half of all known

More information

Biosignals, Chapter 8, rearranged, Part I

Biosignals, Chapter 8, rearranged, Part I Biosignals, Chapter 8, rearranged, Part I Nicotinic Acetylcholine Receptor: A Ligand-Binding Ion Channel Classes of Receptor Proteins in Eukaryotes, Heterotrimeric G Proteins Signaling View the Heterotrimeric

More information

Membrane associated receptor transfers the information. Second messengers relay information

Membrane associated receptor transfers the information. Second messengers relay information Membrane associated receptor transfers the information Most signals are polar and large Few of the signals are nonpolar Receptors are intrinsic membrane proteins Extracellular and intracellular domains

More information

Biochemie 4. Cell communication - GPCR

Biochemie 4. Cell communication - GPCR Biochemie 4 Cell communication - GPCR 1 Lecture outline General principles - local and long-distance signaling - classes of receptors - molecular switches and second messengers Receptor tyrosine kinases

More information

Lecture: CHAPTER 13 Signal Transduction Pathways

Lecture: CHAPTER 13 Signal Transduction Pathways Lecture: 10 17 2016 CHAPTER 13 Signal Transduction Pathways Chapter 13 Outline Signal transduction cascades have many components in common: 1. Release of a primary message as a response to a physiological

More information

FUNDAMENTALS OF BIOCHEMISTRY, CELL BIOLOGY AND BIOPHYSICS Vol. I - Biochemistry of Vitamins, Hormones and Other Messenger Molecules - Chris Whiteley

FUNDAMENTALS OF BIOCHEMISTRY, CELL BIOLOGY AND BIOPHYSICS Vol. I - Biochemistry of Vitamins, Hormones and Other Messenger Molecules - Chris Whiteley BIOCHEMISTRY OF VITAMINS, HORMONES AND OTHER MESSENGER MOLECULES Chris Whiteley Department of Biochemistry and Microbiology, Rhodes University, Grahamstown, South Africa Keywords: phosphorylation, phosphorylase,

More information

G-Protein Signaling. Introduction to intracellular signaling. Dr. SARRAY Sameh, Ph.D

G-Protein Signaling. Introduction to intracellular signaling. Dr. SARRAY Sameh, Ph.D G-Protein Signaling Introduction to intracellular signaling Dr. SARRAY Sameh, Ph.D Cell signaling Cells communicate via extracellular signaling molecules (Hormones, growth factors and neurotransmitters

More information

Chapter 20. Cell - Cell Signaling: Hormones and Receptors. Three general types of extracellular signaling. endocrine signaling. paracrine signaling

Chapter 20. Cell - Cell Signaling: Hormones and Receptors. Three general types of extracellular signaling. endocrine signaling. paracrine signaling Chapter 20 Cell - Cell Signaling: Hormones and Receptors Three general types of extracellular signaling endocrine signaling paracrine signaling autocrine signaling Endocrine Signaling - signaling molecules

More information

MCB*4010 Midterm Exam / Winter 2008

MCB*4010 Midterm Exam / Winter 2008 MCB*4010 Midterm Exam / Winter 2008 Name: ID: Instructions: Answer all 4 questions. The number of marks for each question indicates how many points you need to provide. Write your answers in point form,

More information

Chapter 15: Signal transduction

Chapter 15: Signal transduction Chapter 15: Signal transduction Know the terminology: Enzyme-linked receptor, G-protein linked receptor, nuclear hormone receptor, G-protein, adaptor protein, scaffolding protein, SH2 domain, MAPK, Ras,

More information

Regulation of cell function by intracellular signaling

Regulation of cell function by intracellular signaling Regulation of cell function by intracellular signaling Objectives: Regulation principle Allosteric and covalent mechanisms, Popular second messengers, Protein kinases, Kinase cascade and interaction. regulation

More information

Tala Saleh. Ahmad Attari. Mamoun Ahram

Tala Saleh. Ahmad Attari. Mamoun Ahram 23 Tala Saleh Ahmad Attari Minna Mushtaha Mamoun Ahram In the previous lecture, we discussed the mechanisms of regulating enzymes through inhibitors. Now, we will start this lecture by discussing regulation

More information

Lecture 15. Signal Transduction Pathways - Introduction

Lecture 15. Signal Transduction Pathways - Introduction Lecture 15 Signal Transduction Pathways - Introduction So far.. Regulation of mrna synthesis Regulation of rrna synthesis Regulation of trna & 5S rrna synthesis Regulation of gene expression by signals

More information

Principles of cell signaling Lecture 4

Principles of cell signaling Lecture 4 Principles of cell signaling Lecture 4 Johan Lennartsson Molecular Cell Biology (1BG320), 2014 Johan.Lennartsson@licr.uu.se 1 Receptor tyrosine kinase-induced signal transduction Erk MAP kinase pathway

More information

Effects of Second Messengers

Effects of Second Messengers Effects of Second Messengers Inositol trisphosphate Diacylglycerol Opens Calcium Channels Binding to IP 3 -gated Channel Cooperative binding Activates Protein Kinase C is required Phosphorylation of many

More information

Cell Communication. Chapter 11. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

Cell Communication. Chapter 11. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

BCOR 011 Lecture 19 Oct 12, 2005 I. Cell Communication Signal Transduction Chapter 11

BCOR 011 Lecture 19 Oct 12, 2005 I. Cell Communication Signal Transduction Chapter 11 BCOR 011 Lecture 19 Oct 12, 2005 I. Cell Communication Signal Transduction Chapter 11 External signal is received and converted to another form to elicit a response 1 Lecture Outline 1. Types of intercellular

More information

KEY CONCEPT QUESTIONS IN SIGNAL TRANSDUCTION

KEY CONCEPT QUESTIONS IN SIGNAL TRANSDUCTION Signal Transduction - Part 2 Key Concepts - Receptor tyrosine kinases control cell metabolism and proliferation Growth factor signaling through Ras Mutated cell signaling genes in cancer cells are called

More information

BIOLOGY. Cell Communication CAMPBELL. Reece Urry Cain Wasserman Minorsky Jackson. Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick

BIOLOGY. Cell Communication CAMPBELL. Reece Urry Cain Wasserman Minorsky Jackson. Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson 11 Cell Communication Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick Cellular Messaging Cells can signal to

More information

Chapter 11. Cell Communication

Chapter 11. Cell Communication Chapter 11 Cell Communication Overview: The Cellular Internet Cell-to-cell communication Is absolutely essential for multicellular organisms Concept 11.1: External signals are converted into responses

More information

Cell Communication. Chapter 11. PowerPoint Lectures for Biology, Seventh Edition. Lectures by Chris Romero. Neil Campbell and Jane Reece

Cell Communication. Chapter 11. PowerPoint Lectures for Biology, Seventh Edition. Lectures by Chris Romero. Neil Campbell and Jane Reece Chapter 11 Cell Communication PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Overview: The Cellular Internet Cell-to-cell communication Is absolutely

More information

Vets 111/Biov 111 Cell Signalling-2. Secondary messengers the cyclic AMP intracellular signalling system

Vets 111/Biov 111 Cell Signalling-2. Secondary messengers the cyclic AMP intracellular signalling system Vets 111/Biov 111 Cell Signalling-2 Secondary messengers the cyclic AMP intracellular signalling system The classical secondary messenger model of intracellular signalling A cell surface receptor binds

More information

Chapter 9. Cellular Signaling

Chapter 9. Cellular Signaling Chapter 9 Cellular Signaling Cellular Messaging Page 215 Cells can signal to each other and interpret the signals they receive from other cells and the environment Signals are most often chemicals The

More information

Biol220 Cell Signalling Cyclic AMP the classical secondary messenger

Biol220 Cell Signalling Cyclic AMP the classical secondary messenger Biol220 Cell Signalling Cyclic AMP the classical secondary messenger The classical secondary messenger model of intracellular signalling A cell surface receptor binds the signal molecule (the primary

More information

The Tissue Engineer s Toolkit

The Tissue Engineer s Toolkit The Tissue Engineer s Toolkit Stimuli Detection and Response Ken Webb, Ph. D. Assistant Professor Dept. of Bioengineering Clemson University Environmental Stimulus-Cellular Response Environmental Stimuli

More information

Enzyme-coupled Receptors. Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors

Enzyme-coupled Receptors. Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors Enzyme-coupled Receptors Cell-surface receptors 1. Ion-channel-coupled receptors 2. G-protein-coupled receptors 3. Enzyme-coupled receptors Cell-surface receptors allow a flow of ions across the plasma

More information

Lecture 9: Cell Communication I

Lecture 9: Cell Communication I 02.05.10 Lecture 9: Cell Communication I Multicellular organisms need to coordinate cellular functions in different tissues Cell-to-cell communication is also used by single celled organisms to signal

More information

Signal Transduction: Information Metabolism. Chem 454: Regulatory Mechanisms in Biochemistry University of Wisconsin-Eau Claire

Signal Transduction: Information Metabolism. Chem 454: Regulatory Mechanisms in Biochemistry University of Wisconsin-Eau Claire Signal Transduction: Information Metabolism Chem 454: Regulatory Mechanisms in Biochemistry University of Wisconsin-Eau Claire Introduction Information Metabolism How cells receive, process and respond

More information

Tuesday, Sept. 14, Is an enzyme a rigid system?

Tuesday, Sept. 14, Is an enzyme a rigid system? Tuesday, Sept. 14, Is an enzyme a rigid system? Early researchers thought of enzymes as rigid entities, recognizing their substrates the way a lock would recognize a key. Today's researchers, however,

More information

Chapter 11: Enzyme Catalysis

Chapter 11: Enzyme Catalysis Chapter 11: Enzyme Catalysis Matching A) high B) deprotonated C) protonated D) least resistance E) motion F) rate-determining G) leaving group H) short peptides I) amino acid J) low K) coenzymes L) concerted

More information

Revision. camp pathway

Revision. camp pathway االله الرحمن الرحيم بسم Revision camp pathway camp pathway Revision camp pathway Adenylate cyclase Adenylate Cyclase enzyme Adenylate cyclase catalyses the formation of camp from ATP. Stimulation or inhibition

More information

Asma Karameh BAHAA NAJJAR. Ebaa' Alzayadneh

Asma Karameh BAHAA NAJJAR. Ebaa' Alzayadneh 26 Asma Karameh BAHAA NAJJAR Ebaa' Alzayadneh Generally speaking, all cells have been programmed during development to response to specific set of extracellular signals produced by other cells.these signals

More information

GPCR. General Principles of Cell Signaling G-protein-Coupled Receptors Enzyme-Coupled Receptors Other Signaling Pathways. G-protein-Coupled Receptors

GPCR. General Principles of Cell Signaling G-protein-Coupled Receptors Enzyme-Coupled Receptors Other Signaling Pathways. G-protein-Coupled Receptors G-protein-Coupled Receptors General Principles of Cell Signaling G-protein-Coupled Receptors Enzyme-Coupled Receptors Other Signaling Pathways GPCR G-protein-coupled receptors Figure 15-30 Molecular Biology

More information

Plasma membranes. Plasmodesmata between plant cells. Gap junctions between animal cells Cell junctions. Cell-cell recognition

Plasma membranes. Plasmodesmata between plant cells. Gap junctions between animal cells Cell junctions. Cell-cell recognition Cell Communication Cell Signaling Cell-to-cell communication is essential for multicellular organisms Communicate by chemical messengers Animal and plant cells have cell junctions that directly connect

More information

Cell Biology Lecture 9 Notes Basic Principles of cell signaling and GPCR system

Cell Biology Lecture 9 Notes Basic Principles of cell signaling and GPCR system Cell Biology Lecture 9 Notes Basic Principles of cell signaling and GPCR system Basic Elements of cell signaling: Signal or signaling molecule (ligand, first messenger) o Small molecules (epinephrine,

More information

Cell Communication. Chapter 11. Biology. Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

Cell Communication. Chapter 11. Biology. Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

Cell Communication. Local and Long Distance Signaling

Cell Communication. Local and Long Distance Signaling Cell Communication Cell to cell communication is essential for multicellular organisms Some universal mechanisms of cellular regulation providing more evidence for the evolutionary relatedness of all life

More information

- Biosignaling: Signal transduction. References: chapter 8 of Lippincots chapter 1 3 of Lehningers

- Biosignaling: Signal transduction. References: chapter 8 of Lippincots chapter 1 3 of Lehningers Basic concepts of Metabolism Metabolism and metabolic pathway Metabolic Map Catabolism Anabolism - Regulation of Metabolism Signals from within the cell (Intracellular) Communication between cells. - Biosignaling:

More information

Introduction! Introduction! Introduction! Chem Lecture 10 Signal Transduction & Sensory Systems Part 2

Introduction! Introduction! Introduction! Chem Lecture 10 Signal Transduction & Sensory Systems Part 2 Chem 452 - Lecture 10 Signal Transduction & Sensory Systems Part 2 Questions of the Day: How does the hormone insulin trigger the uptake of glucose in the cells that it targets. Introduction! Signal transduction

More information

Cell Communication. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

Cell Communication. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

Cell Communication. Chapter 11. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

Cell Communication. Chapter 11. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

ANATOMY & PHYSIOLOGY - CLUTCH CH. 6 - CELL COMMUNICATION.

ANATOMY & PHYSIOLOGY - CLUTCH CH. 6 - CELL COMMUNICATION. !! www.clutchprep.com CONCEPT: CELL-TO-CELL CONNECTIONS AND SIGNALING Gap and Tight Junctions: Adjacent cells communicate and hold on to each other via junctions. Two important kinds: Gap Junctions are

More information

Hormones and Signal Transduction. Dr. Kevin Ahern

Hormones and Signal Transduction. Dr. Kevin Ahern Dr. Kevin Ahern Signaling Outline Signaling Outline Background Signaling Outline Background Membranes Signaling Outline Background Membranes Hormones & Receptors Signaling Outline Background Membranes

More information

Cellular Signaling Pathways. Signaling Overview

Cellular Signaling Pathways. Signaling Overview Cellular Signaling Pathways Signaling Overview Signaling steps Synthesis and release of signaling molecules (ligands) by the signaling cell. Transport of the signal to the target cell Detection of the

More information

Cell Communication. Chapter 11. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

Cell Communication. Chapter 11. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

PHSI3009 Frontiers in Cellular Physiology 2017

PHSI3009 Frontiers in Cellular Physiology 2017 Overview of PHSI3009 L2 Cell membrane and Principles of cell communication L3 Signalling via G protein-coupled receptor L4 Calcium Signalling L5 Signalling via Growth Factors L6 Signalling via small G-protein

More information

Lecture 34. Carbohydrate Metabolism 2. Glycogen. Key Concepts. Biochemistry and regulation of glycogen degradation

Lecture 34. Carbohydrate Metabolism 2. Glycogen. Key Concepts. Biochemistry and regulation of glycogen degradation Lecture 34 Carbohydrate Metabolism 2 Glycogen Key Concepts Overview of Glycogen Metabolism Biochemistry and regulation of glycogen degradation Biochemistry and regulation of glycogen synthesis What mechanisms

More information

Signal Transduction I

Signal Transduction I Signal Transduction I Prof. Tianhua Zhou Department of Cell Biology Zhejiang University School of Medicine Office hours by appointment tzhou@zju.edu.cn Signal transduction: Key contents for signal transduction:

More information

Chapter 11 Cell Communication Guided Reading. 3. How do intercellular connections function in cell to cell communication?

Chapter 11 Cell Communication Guided Reading. 3. How do intercellular connections function in cell to cell communication? AP Biology TEXT: Biology, Campbell and Reece 7 th Edition Name Chapter 11 Cell Communication Guided Reading This chapter is often considered difficult as you have not covered it in an introductory biology

More information

BIOLOGY. Cell Communication CAMPBELL. Reece Urry Cain Wasserman Minorsky Jackson. Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick

BIOLOGY. Cell Communication CAMPBELL. Reece Urry Cain Wasserman Minorsky Jackson. Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson 11 Cell Communication Lecture Presentation by Nicole Tunbridge and Kathleen Fitzpatrick Cellular Messaging Cells can signal to

More information

Revision. General functions of hormones. Hormone receptors. Hormone derived from steroids Small polypeptide Hormone

Revision. General functions of hormones. Hormone receptors. Hormone derived from steroids Small polypeptide Hormone االله الرحمن الرحيم بسم Revision General functions of hormones. Hormone receptors Classification according to chemical nature Classification according to mechanism of action Compare and contrast between

More information

Principles of Genetics and Molecular Biology

Principles of Genetics and Molecular Biology Cell signaling Dr. Diala Abu-Hassan, DDS, PhD School of Medicine Dr.abuhassand@gmail.com Principles of Genetics and Molecular Biology www.cs.montana.edu Modes of cell signaling Direct interaction of a

More information

Chapter 15: Signal transduction

Chapter 15: Signal transduction Chapter 15: Signal transduction Know the terminology: Enzyme-linked receptor IP3+DAG G-protein linked receptor camp nuclear hormone receptor Ca 2+ G-protein adaptor protein protein kinase scaffolding protein

More information

Cell Signaling and Communication - 1

Cell Signaling and Communication - 1 Cell Signaling and Communication - 1 Just as we communicate with other humans in a number of different ways, cells communicate with other cells and with their external environment with a set of cell signal

More information

Chem Lecture 10 Signal Transduction

Chem Lecture 10 Signal Transduction Chem 452 - Lecture 10 Signal Transduction 111130 Here we look at the movement of a signal from the outside of a cell to its inside, where it elicits changes within the cell. These changes are usually mediated

More information

2013 W. H. Freeman and Company. 12 Signal Transduction

2013 W. H. Freeman and Company. 12 Signal Transduction 2013 W. H. Freeman and Company 12 Signal Transduction CHAPTER 12 Signal Transduction Key topics: General features of signal transduction Structure and function of G protein coupled receptors Structure

More information

Cell Communication. Cell Communication. Cell Communication. Cell Communication. Cell Communication. Chapter 9. Communication between cells requires:

Cell Communication. Cell Communication. Cell Communication. Cell Communication. Cell Communication. Chapter 9. Communication between cells requires: Chapter 9 Communication between cells requires: ligand: the signaling molecule receptor protein: the molecule to which the receptor binds -may be on the plasma membrane or within the cell 2 There are four

More information

Molecular Cell Biology - Problem Drill 19: Cell Signaling Pathways and Gene Expression

Molecular Cell Biology - Problem Drill 19: Cell Signaling Pathways and Gene Expression Molecular Cell Biology - Problem Drill 19: Cell Signaling Pathways and Gene Expression Question No. 1 of 10 1. Which statement about cell signaling is correct? Question #1 (A) Cell signaling involves receiving

More information

Chapter 11. Cell Communication. Signal Transduction Pathways

Chapter 11. Cell Communication. Signal Transduction Pathways Chapter 11 Cell Communication Signal Transduction Pathways Signal-Transduction Pathway Signal on a cell s surface is converted into a specific cellular response Local signaling (short distance) - Paracrine

More information

*Today s lecture is from chapter 15 from a book called Stryer the doctor gave us the website:

*Today s lecture is from chapter 15 from a book called Stryer the doctor gave us the website: *Today s lecture is from chapter 15 from a book called Stryer the doctor gave us the website: You can Google it (Pubmed) or www.ncbi.nlm.nih.gov/books/nbk21205/,the book also has lots of medical articles

More information

Receptors and Drug Action. Dr. Subasini Pharmacology Department Ishik University, Erbil

Receptors and Drug Action. Dr. Subasini Pharmacology Department Ishik University, Erbil Receptors and Drug Action Dr. Subasini Pharmacology Department Ishik University, Erbil Receptors and Drug Action Receptor Receptor is defined as a macromolecule or binding site located on the surface or

More information

number Done by Corrected by Doctor Nayef Karadsheh

number Done by Corrected by Doctor Nayef Karadsheh number 15 Done by BaraaAyed Corrected by Mamoon Alqtamin Doctor Nayef Karadsheh 1 P a g e Regulation of glycogen synthesis and degradation Regulation of glycogen synthesis and degradation involves two

More information

INTERACTION DRUG BODY

INTERACTION DRUG BODY INTERACTION DRUG BODY What the drug does to the body What the body does to the drug Receptors - intracellular receptors - membrane receptors - Channel receptors - G protein-coupled receptors - Tyrosine-kinase

More information

A Primer on G Protein Signaling. Elliott Ross UT-Southwestern Medical Center

A Primer on G Protein Signaling. Elliott Ross UT-Southwestern Medical Center A Primer on G Protein Signaling Elliott Ross UT-Southwestern Medical Center Receptor G Effector The MODULE Rhodopsins Adrenergics Muscarinics Serotonin, Dopamine Histamine, GABA b, Glutamate Eiscosanoids

More information

Resp & Cell Comm Review

Resp & Cell Comm Review Resp & Cell Comm Review Two main catabolic processes: fermentation: partial degradation of sugars in the absence of oxygen. cellular respiration: uses oxygen to complete the breakdown of many organic molecules.

More information

MBG301. Class IV. Classification of GPCRs according to their effector function (according to Lodish)

MBG301. Class IV. Classification of GPCRs according to their effector function (according to Lodish) MBG301 Class IV Classification of GPCRs according to their effector function (according to Lodish) 1. Adenylcyclase activation by GPCRs 2. Ion channel regulation by GPCRs 3. Phospholipase C (PLC) activation

More information

G protein-coupled Signal Transduction

G protein-coupled Signal Transduction Theresa Filtz, hd har 735, Winter 2006 G protein-coupled Signal Transduction Main Objectives (the big chunks) Describe in molecular detail the cascades of events in a generalized G protein-coupled signaling

More information

Cell Communication. Cell Communication. Communication between cells requires: ligand: the signaling molecule

Cell Communication. Cell Communication. Communication between cells requires: ligand: the signaling molecule Cell Communication Cell Communication Communication between cells requires: ligand: the signaling molecule receptor protein: the molecule to which the ligand binds (may be on the plasma membrane or within

More information

BL 424 Chapter 15: Cell Signaling; Signal Transduction

BL 424 Chapter 15: Cell Signaling; Signal Transduction BL 424 Chapter 15: Cell Signaling; Signal Transduction All cells receive and respond to signals from their environments. The behavior of each individual cell in multicellular plants and animals must be

More information

Organization of lectures: Cell Signaling I: Sex, Drugs and Violence. Cell signaling is central to modern medicine. Forms of Cell Signaling

Organization of lectures: Cell Signaling I: Sex, Drugs and Violence. Cell signaling is central to modern medicine. Forms of Cell Signaling Cell Signaling I: Sex, Drugs and Violence Joe W. Ramos jramos@crch.hawaii.edu www.crch.org/profiles/jramos Organization of lectures: General Principles of signaling cascades Hormone Signaling Signaling

More information

The elements of G protein-coupled receptor systems

The elements of G protein-coupled receptor systems The elements of G protein-coupled receptor systems Prostaglandines Sphingosine 1-phosphate a receptor that contains 7 membrane-spanning domains a coupled trimeric G protein which functions as a switch

More information

Signaling Through Immune System Receptors (Ch. 7)

Signaling Through Immune System Receptors (Ch. 7) Signaling Through Immune System Receptors (Ch. 7) 1. General principles of signal transduction and propagation. 2. Antigen receptor signaling and lymphocyte activation. 3. Other receptors and signaling

More information

Signal-Transduction Cascades - 2. The Phosphoinositide Cascade

Signal-Transduction Cascades - 2. The Phosphoinositide Cascade Signal-Transduction Cascades - 2 The Phosphoinositide Cascade Calcium ion as a second messenger Tyrosine kinase and receptor dimerization scribd.com Faisal Khatib JU The Phosphoinositide Cascade Used by

More information

Lecture 36: Review of membrane function

Lecture 36: Review of membrane function Chem*3560 Lecture 36: Review of membrane function Membrane: Lipid bilayer with embedded or associated proteins. Bilayers: 40-70% neutral phospholipid 10-20% negative phospholipid 10-30% cholesterol 10-30%

More information

Model Answer. M.Sc. Zoology (First Semester) Examination Paper LZT 103 (Endocrinology)

Model Answer. M.Sc. Zoology (First Semester) Examination Paper LZT 103 (Endocrinology) Model Answer M.Sc. Zoology (First Semester) Examination-2013 Paper LZT 103 (Endocrinology) Section A 1. (i) d (ii) b (iii) b (iv) c (v) c (vi) a (vii) c (viii) a (ix) d (x) b Section B Q.2 Answer Hormonal

More information

Chapter 10. Introduction to Nutrition and Metabolism, 3 rd edition David A Bender Taylor & Francis Ltd, London 2002

Chapter 10. Introduction to Nutrition and Metabolism, 3 rd edition David A Bender Taylor & Francis Ltd, London 2002 Chapter 10 Introduction to Nutrition and Metabolism, 3 rd edition David A Bender Taylor & Francis Ltd, London 2002 Chapter 10: Integration and Control of Metabolism Press the space bar or click the mouse

More information

Cell Communication. Chapter 11. Biology. Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

Cell Communication. Chapter 11. Biology. Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 11 Cell Communication PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

Final Review Sessions. 3/16 (FRI) 126 Wellman (4-6 6 pm) 3/19 (MON) 1309 Surge 3 (4-6 6 pm) Office Hours

Final Review Sessions. 3/16 (FRI) 126 Wellman (4-6 6 pm) 3/19 (MON) 1309 Surge 3 (4-6 6 pm) Office Hours Final Review Sessions 3/16 (FRI) 126 Wellman (4-6 6 pm) 3/19 (MON) 1309 Surge 3 (4-6 6 pm) Office ours 3/14 (WED) 9:30 11:30 am (Rebecca) 3/16 (FRI) 9-11 am (Abel) Final ESSENTIALS Posted Lecture 20 ormonal

More information

number Done by Corrected by Doctor Nayef Karadsheh

number Done by Corrected by Doctor Nayef Karadsheh number 11 Done by حسام أبو عوض Corrected by Moayyad Al-Shafei Doctor Nayef Karadsheh 1 P a g e General Regulatory Aspects in Metabolism: We can divide all pathways in metabolism to catabolicand anabolic.

More information

Cell Communication - 1

Cell Communication - 1 Cell Communication - 1 Just as we communicate with other humans (a number of different ways), cells communicate with other cells, to interact with the external environment and to make appropriate responses

More information

Zaid sarhan. Osama Al-Ghafri ... Dr.nayef karadsheh

Zaid sarhan. Osama Al-Ghafri ... Dr.nayef karadsheh 16 Zaid sarhan Osama Al-Ghafri... Dr.nayef karadsheh ALL THE FIGUERS IN THIS SHEET ARE VERY IMPORTANT AND USEFUL, PLEASE DON T SKIP THEM. Glycogen phosphorylase kinase = GPK // glycogen phosphorylase=gp

More information

G-Protein Coupled Receptors GPCRs. GPCRs

G-Protein Coupled Receptors GPCRs. GPCRs 2 type of ligands 1 G-Protein Coupled Receptors GPCRs One of the largest protein families: > 1000 type of GPCRs in mammals >3% of the human genes Major drug targets: ~ 60 % of approved drugs interact with

More information

LECTURE PRESENTATIONS

LECTURE PRESENTATIONS LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson Chapter 11 Cell Communication Lectures

More information

Physiology Unit 1 CELL SIGNALING: CHEMICAL MESSENGERS AND SIGNAL TRANSDUCTION PATHWAYS

Physiology Unit 1 CELL SIGNALING: CHEMICAL MESSENGERS AND SIGNAL TRANSDUCTION PATHWAYS Physiology Unit 1 CELL SIGNALING: CHEMICAL MESSENGERS AND SIGNAL TRANSDUCTION PATHWAYS In Physiology Today Cell Communication Homeostatic mechanisms maintain a normal balance of the body s internal environment

More information

2402 : Anatomy/Physiology

2402 : Anatomy/Physiology Dr. Chris Doumen Lecture 2 2402 : Anatomy/Physiology The Endocrine System G proteins and Adenylate Cyclase /camp TextBook Readings Pages 405 and 599 through 603. Make use of the figures in your textbook

More information

What would you observe if you fused a G1 cell with a S cell? A. Mitotic and pulverized chromosomes. B. Mitotic and compact G1 chromosomes.

What would you observe if you fused a G1 cell with a S cell? A. Mitotic and pulverized chromosomes. B. Mitotic and compact G1 chromosomes. What would you observe if you fused a G1 cell with a S cell? A. Mitotic and pulverized chromosomes. B. Mitotic and compact G1 chromosomes. C. Mostly non-compact G1 chromosomes. D. Compact G1 and G2 chromosomes.

More information

Which DNA sequence is most likely to form a hairpin structure? x indicates any nucleotide.

Which DNA sequence is most likely to form a hairpin structure? x indicates any nucleotide. Which DNA sequence is most likely to form a hairpin structure? x indicates any nucleotide. A. xxxgtcagtxxxxtatgcgxxx B. xxxtcgtatxxxxgtccgaxxx C. xxxcactgtxxxxgtactgxxx D. xxxgtcagtxxxxcctagaxxx E. xxxgtcatcxxxxgatgacxxx

More information

Regulation of Enzymatic Activity. Lesson 4

Regulation of Enzymatic Activity. Lesson 4 Regulation of Enzymatic Activity Lesson 4 Regulation of Enzymatic Activity no real regulation: - regulation of enzyme expression and turnover - control of enzyme trafficking - supply of cofactors real

More information

Ras and Cell Signaling Exercise

Ras and Cell Signaling Exercise Ras and Cell Signaling Exercise Learning Objectives In this exercise, you will use, a protein 3D- viewer, to explore: the structure of the Ras protein the active and inactive state of Ras and the amino

More information

Copyright Mark Brandt, Ph.D. 128

Copyright Mark Brandt, Ph.D. 128 Signal transduction In order to interact properly with their environment, cells need to allow information as well as molecules to cross their cell membranes. Information in many single-celled and all multicellular

More information

Cell signaling. How do cells receive and respond to signals from their surroundings?

Cell signaling. How do cells receive and respond to signals from their surroundings? Cell signaling How do cells receive and respond to signals from their surroundings? Prokaryotes and unicellular eukaryotes are largely independent and autonomous. In multicellular organisms there is a

More information

1. Activated receptor tyrosine kinases (RTKs) phosphorylates themselves

1. Activated receptor tyrosine kinases (RTKs) phosphorylates themselves Enzyme-coupled receptors Transmembrane proteins Ligand-binding domain on the outer surface Cytoplasmic domain acts as an enzyme itself or forms a complex with enzyme 1. Activated receptor tyrosine kinases

More information