Hormones and Signal Transduction. Dr. Kevin Ahern

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1 Dr. Kevin Ahern

2 Signaling Outline

3 Signaling Outline Background

4 Signaling Outline Background Membranes

5 Signaling Outline Background Membranes Hormones & Receptors

6 Signaling Outline Background Membranes Hormones & Receptors Second Messengers

7 Signaling Introduction

8 Signaling Introduction Needs of a Multicellular Organism

9 Signaling Introduction Needs of a Multicellular Organism Responding to Environment

10 Signaling Introduction Needs of a Multicellular Organism Responding to Environment Food Status

11 Signaling Introduction Needs of a Multicellular Organism Responding to Environment Food Status Danger

12 Signaling Introduction Needs of a Multicellular Organism Responding to Environment Food Status Danger Growth

13 Signaling Introduction Needs of a Multicellular Organism Responding to Environment Food Status Danger Growth Injury

14 Signaling Introduction Coordination of Cellular/Tissue Responses

15 Signaling Introduction Coordination of Cellular/Tissue Responses

16 Signaling

17 Signaling Membranes Organization of Bilayer Around Cell

18 Signaling Membranes Lipid Bilayer Prevents Entry of Most Molecules Organization of Bilayer Around Cell

19 Signaling Membranes Lipid Bilayer Prevents Entry of Most Molecules Lipid Bilayer Organization of Bilayer Around Cell

20 Signaling Membranes Lipid Bilayer Prevents Entry of Most Molecules Lipid Bilayer Organization of Bilayer Around Cell

21 Signaling Membranes Lipid Bilayer Prevents Entry of Most Molecules Lipid Bilayer Organization of Bilayer Around Cell Information must move across membrane

22 Signaling Membranes Lipid Bilayer Prevents Entry of Most Molecules Lipid Bilayer Organization of Bilayer Around Cell Information must move across membrane Signal Transduction

23 Signaling

24 Signaling Simplest Signaling

25 Signaling Simplest Signaling Signal

26 Signaling Simplest Signaling Signal Response

27 Nerve System Signaling

28 Hormones

29 Hormones Hormones Communicate Messages

30 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body

31 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body

32 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body First Messengers of a Multi-component Message

33 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body First Messengers of a Multi-component Message Numerous Chemical Forms

34 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body First Messengers of a Multi-component Message Numerous Chemical Forms Thyroid Hormone

35 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body First Messengers of a Multi-component Message Numerous Chemical Forms Thyroid Hormone Epinephrine

36 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body First Messengers of a Multi-component Message Numerous Chemical Forms Thyroid Hormone Epinephrine Epidermal Growth Factor

37 Hormones Hormones Communicate Messages Hormones are Made in One Part of the Body Exert Effects in Other Part of Body First Messengers of a Multi-component Message Numerous Chemical Forms Thyroid Hormone Epinephrine Epidermal Growth Factor Progesterone

38 Introduction

39 Introduction Cellular Signaling Has Complexity

40 Introduction Cellular Signaling Has Complexity Responses Aimed at Benefitting Organism

41

42 Binding to Receptor

43 Binding to Receptor

44 Binding to Receptor Steroid Hormones Diffuse Through Membrane

45 Binding to Receptor Steroid Hormones Diffuse Through Membrane Cytosolic Receptor

46 Binding to Receptor Steroid Hormones Diffuse Through Membrane Cytosolic Receptor Receptor Binding Inside Cell

47 Binding to Receptor Steroid Hormones Diffuse Through Membrane Cytosolic Receptor Receptor Binding Inside Cell

48 Binding to Receptor Non-steroid Hormone Steroid Hormones Diffuse Through Membrane Cytosolic Receptor Receptor Binding Inside Cell

49 Binding to Receptor Receptor Binding Outside of Cell Non-steroid Hormone Steroid Hormones Diffuse Through Membrane Cytosolic Receptor Receptor Binding Inside Cell

50 Receptor Binding Outside of Cell Hormones and Signal Transduction Binding to Receptor Non-steroid Hormone Numerous Internal Message Carriers Steroid Hormones Diffuse Through Membrane Cytosolic Receptor Receptor Binding Inside Cell

51 Receptors

52 Receptors Interaction of Hormone with Receptor Changes Receptor

53 Receptors Interaction of Hormone with Receptor Changes Receptor Receptor Change Alters Interactions with Other Proteins

54 Receptors Interaction of Hormone with Receptor Changes Receptor Receptor Change Alters Interactions with Other Proteins Changes on Hormone Binding

55 Membrane-bound Receptors G-Protein Coupled Receptor

56 G-protein Coupled Receptors (GPCRs)

57 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome

58 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome 460 Olfactory

59 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome 460 Olfactory β-adrenergic Receptor

60 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome 460 Olfactory β-adrenergic Receptor Membrane Bound

61 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome 460 Olfactory β-adrenergic Receptor Membrane Bound Seven Transmembrane Domains

62 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome 460 Olfactory β-adrenergic Receptor Extracellular Domain Membrane Bound Seven Transmembrane Domains

63 G-protein Coupled Receptors (GPCRs) Almost 800 Genes in Human Genome 460 Olfactory β-adrenergic Receptor Extracellular Domain Intracellular Domain Membrane Bound Seven Transmembrane Domains

64 GPCR Action Cycle

65 GPCR Action Cycle

66

67 Hormone

68 Hormone Binding of Hormone

69 Binding of Hormone Hormone Structural Change of Receptor

70 Binding of Hormone Hormone Structural Change of Receptor Replacement of GDP by GTP

71 Binding of Hormone Hormone Structural Change of Receptor Activation of an Enzyme Replacement of GDP by GTP

72 Binding of Hormone Hormone Structural Change of Receptor Return to Original State Activation of an Enzyme Replacement of GDP by GTP

73 Receipt of Message

74 Receipt of Message Membrane Receptor Proteins Internalize Message

75 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers

76 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Inositol 1,4,5 Trisphosphate (IP3)

77 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Inositol 1,4,5 Trisphosphate (IP3) Cyclic AMP (camp)

78 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Inositol 1,4,5 Trisphosphate (IP3) Ca ++ Ca ++ Ca ++ Ca++ Ca Ca Cyclic AMP (camp) Calcium Ions

79 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Inositol 1,4,5 Trisphosphate (IP3) Ca ++ Ca ++ Ca ++ Ca++ Ca Ca Cyclic AMP (camp) Calcium Ions Cyclic GMP (cgmp)

80 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Covalent Modification of Downstream Proteins Inositol 1,4,5 Trisphosphate (IP3) Ca ++ Ca ++ Ca ++ Ca++ Ca Ca Cyclic AMP (camp) Calcium Ions Cyclic GMP (cgmp)

81 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Covalent Modification of Downstream Proteins Alteration of Gene Expression Inositol 1,4,5 Trisphosphate (IP3) Ca ++ Ca ++ Ca ++ Ca++ Ca Ca Cyclic AMP (camp) Calcium Ions Cyclic GMP (cgmp)

82 Receipt of Message Membrane Receptor Proteins Internalize Message Activate Synthesis of Second Messengers Covalent Modification of Downstream Proteins Alteration of Gene Expression Change of Enzyme Activities Inositol 1,4,5 Trisphosphate (IP3) Ca ++ Ca ++ Ca ++ Ca++ Ca Ca Cyclic AMP (camp) Calcium Ions Cyclic GMP (cgmp)

83 GPCRs and G-Proteins

84 GPCRs and G-Proteins GPCR β γ

85 GPCRs and G-Proteins GPCR Resting State β γ

86 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) GPCR Resting State β γ

87 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits GPCR Resting State β γ

88 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits Associate with GPCRs GPCR Resting State β γ

89 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits Associate with GPCRs Altered by GPCR s Binding of Hormone GPCR Resting State β γ

90 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits Associate with GPCRs Altered by GPCR s Binding of Hormone GPCR β γ Resting State Epinephrine

91 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits Associate with GPCRs Altered by GPCR s Binding of Hormone Epinephrine Epinephrine β γ GPCR β γ GPCR Resting State

92 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits Associate with GPCRs Altered by GPCR s Binding of Hormone Epinephrine Epinephrine β γ GPCR β γ GPCR Resting State GTP GDP

93 GPCRs and G-Proteins G-Proteins Bind Guanine Nucleotides (GDP and GTP) Heterotrimeric - α,β,γ Subunits Associate with GPCRs Altered by GPCR s Binding of Hormone GPCR Epinephrine β γ Epinephrine β γ GPCR Epinephrine GPCR + Resting State β γ GTP GDP Active

94 β-adrenergic Receptor Signaling Creation of the Second Messenger

95 β-adrenergic Receptor Signaling Creation of the Second Messenger

96 β-adrenergic Receptor Signaling Creation of the Second Messenger Adenylate Cyclase

97 β-adrenergic Receptor Signaling Creation of the Second Messenger Adenylate Cyclase Also Membrane Bound

98 β-adrenergic Receptor Signaling Creation of the Second Messenger Adenylate Cyclase Adenylate Cyclase Also Membrane Bound

99 β-adrenergic Receptor Signaling Creation of the Second Messenger Adenylate Cyclase Adenylate Cyclase Also Membrane Bound Activated by binding to α-subunit of G-protein

100 β-adrenergic Receptor Signaling Creation of the Second Messenger ATP Adenylate Cyclase Adenylate Cyclase camp + PPi Also Membrane Bound Activated by binding to α-subunit of G-protein

101 β-adrenergic Receptor Signaling Creation of the Second Messenger Adenylate Cyclase Adenylate Cyclase ATP Second Messenger camp + PPi Also Membrane Bound Activated by binding to α-subunit of G-protein

102 β-adrenergic Receptor Signaling Creation of the Second Messenger Adenylate Cyclase Adenylate Cyclase ATP Second Messenger camp + PPi Also Membrane Bound Activated by binding to α-subunit of G-protein Transmits Signal

103 Actions of the Second Messenger 4 camp

104 Actions of the Second Messenger Protein Kinase A 4 camp

105 Actions of the Second Messenger Protein Kinase A 4 camp (Inactive)

106 Actions of the Second Messenger Protein Kinase A 4 camp (Inactive)

107 Actions of the Second Messenger Catalytic Subunits Protein Kinase A 4 camp (Inactive)

108 Actions of the Second Messenger Regulatory Subunits Catalytic Subunits Protein Kinase A 4 camp (Inactive)

109 Actions of the Second Messenger Protein Kinase A 4 camp Activated (Inactive)

110 Actions of the Second Messenger Protein Kinase A 4 camp Activated (Inactive)

111 Actions of the Second Messenger Protein Kinase A (Inactive) 4 camp Activated Activity Altered by Phosphorylation

112 Metabolic Melody

113 The Tao of Hormones (To the tune of "The Sound of Silence") Copyright Kevin Ahern Metabolic Melody

114 The Tao of Hormones (To the tune of "The Sound of Silence") Copyright Kevin Ahern Biochemistry my friend It's time to study you again Mechanisms that I need to know Are the things that really stress me so "Get these pathways planted firmly in your head," Ahern said Let's start with ep-inephrine Membrane proteins are well known Changed on binding this hormone Rearranging selves without protest Stimulating a G alpha S To go open up and displace its GDP With GTP Because of ep-inephrine Active G then moves a ways Stimulating ad cyclase So a bunch of cyclic AMP Binds to kinase and then sets it free All the active sites of the kinases await Triphosphate Because of ep-inephrine

115 The Tao of Hormones (To the tune of "The Sound of Silence") Copyright Kevin Ahern Biochemistry my friend It's time to study you again Mechanisms that I need to know Are the things that really stress me so "Get these pathways planted firmly in your head," Ahern said Let's start with ep-inephrine Membrane proteins are well known Changed on binding this hormone Rearranging selves without protest Stimulating a G alpha S To go open up and displace its GDP With GTP Because of ep-inephrine Active G then moves a ways Stimulating ad cyclase So a bunch of cyclic AMP Binds to kinase and then sets it free All the active sites of the kinases await Triphosphate Because of ep-inephrine Muscles are affected then Breaking down their glycogen So they get a wad of energy In the form of lots of G-1-P And the synthases that could make a glucose chain All refrain Because of ep-inephrine Now I've reached the pathway end Going from adrenalin Here's a trick I learned to get it right Linking memory to flight or fright So the mechanism that's the source of anxious fears Reappears When I make ep-inephrine

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