Kinases and Pseudokinases: Spines, Scaffolds and Molecular Switches

Transcription

1 Symposium Schedule Saturday, December 5, :00 pm 7:00 pm Participant check-in, badge and program pick-up 5:30 pm 7:00 pm Welcome Reception 7:00 pm 9:00 pm Session 1 Expanding World of Protein Phosphorylation Chair: Jack Dixon, UCSD 7:00 pm -7:10 pm Welcome and Introduction Susan Taylor, UCSD 7:10 pm - 8:10 pm The kinome turns thirty: What have we learned about the (pseudo)kinase family since 1985? Tony Hunter, Salk Institute for Biological Studies 8:10 pm - 8:30 pm Phosphorylation of secreted proteins by a new family of kinases Vincent Tagliabracci, UT Southwestern Medical Center 8:30 pm - 9:00 pm Evolution of kinase catalytic and regulatory functions and implications for predicting causative disease mutations Kannan Natarajan, University of Georgia

2 Sunday, December 6, :00 am 8:15 am Breakfast 8:30 am 12:30 pm Session 2 Spines, Dynamics and Allostery Chair: Susan Taylor, UCSD 8:30 am - 9:00 am Dynamics driven allostery in protein kinases Alexandr Kornev. UCSD 9:00 am - 9:30 am Control of enzyme activity and inhibition of the MAP kinase, ERK2, by protein dynamics Natalie Ahn, University of Colorado 9:30 am - 9:45 am Structural and dynamic aspects of docking-mediated substrate phosphorylation by ERK2 Ranajeet Ghose, City College of New York 9:45 am - 10:00 am Signaling in the catalytic subunit of protein kinase A via hydrophobic motifs Jonggul Kim, University of Minnesota 10:00 am - 10:30 am Allosteric regulation and inhibition of Src kinase Marcus Seeliger, Stony Brook University 10:30 am - 11:00 am Networking and Coffee Break 11:00 am - 11:30 am The regulatory machinery of the Tec family kinases Amy Andreotti, Iowa State University 11:30 am - 11:45 am Non-canonical functions of EPKs explored by manipulation of their hydrophobic spines Lalima Ahuja, UCSD 11:45 am - 12:00 pm Simulations of FGFR2 kinase activation loop dynamics and their effects on catalytic activity Jerome Karp, Albert Einstein College of Medicine 12:00 pm - 12:30 pm Mob1-dependent activation of the central Mst-Lats kinase cascade in Hippo signaling network Xuelian Sue Luo, UT Southwestern Medical Center

3 Sunday, December 6, 2015, continued 12:30 pm 2:45 pm Attendees on own for lunch and free time 3:00 pm 4:00 pm Poster Session 4:00 pm 6:00 pm Session 3 Catalysts vs. Scaffolds Chair: Andrey Shaw, Washington University in St. Louis School of Medicine 4:00 pm - 4:30 pm The Ys and the wherefores of kinase autoinhibition Richard Bayliss, University of Leicester 4:30 pm - 4:45 pm Discovery and analysis of Tribbles 2 pseudokinase ligands Patrick Eyers, University of Liverpool 4:45 pm - 5:15 pm Evolution of the MLKL pseudokinase domain as a suppressor of cell death by necroptosis James Murphy, Walter and Eliza Hall Institute of Medical Research 5:15 pm - 5:30 pm MD Simulations of mutated kinases reveal structural insights into functional consequences Natalie Stephenson, Cancer Research UK Manchester Institute, University of Manchester 5:30 pm - 6:00 pm Allosteric regulation of the anchored protein kinase A holoenzyme: are the catalytic subunits released in situ? John Scott, University of Washington 6:00 pm - 8:00 pm Networking Dinner Sunday evening s program continues following dinner.

4 Sunday, December 6, 2015, continued 8:00 pm 10:00 pm Session 4 Pseudokinases in Tandem Domain Arrays Chair: James Murphy, Walter and Eliza Hall Institute of Medical Research 8:00 pm - 8:30 pm Regulatory roles of the JAK2 pseudokinase domain in normal and pathologic signaling Stevan Hubbard, New York University 8:30 pm - 8:45 pm Pseudokinase domain mutations in JAK2 dictate aberrant cytokine receptor signaling repertoire in myeloproliferative neoplasm Lily Huang, UT Southwestern Medical Center 8:45 pm - 9:15 pm Structure of the pseudokinase kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition Patrick Lupardus, Genentech, Inc. 9:15 pm - 9:30 pm Uncoupling V617F- from cytokine-induced activation of JAK2 by charge changes along the JH2 α helix C Emilie Leroy, Ludwig Cancer Research, de Duve Institute 9:30 pm - 10:00 pm Mutation of a conserved lysine in the kinase homology domain reduces the natriuretic peptide-dependent activity and phosphorylation of guanylyl cyclase-a Lincoln Potter, University of Minnesota

5 Monday, December 7, :00 am 8:15 am Breakfast 8:30 am 12:30 pm Session 5 Dimers and Allostery Chair: Dario Alessi, University of Dundee 8:30 am - 9:00 am Talk tba Andrey Shaw, Washington University in St. Louis School of Medicine 9:00 am - 9:15 am Regulation of cell death by kinase RIPK1 Kim Newton, Genentech, Inc. 9:15 am - 9:45 am Positive feedback through the RHO GEF GEF-H1 regulates KSR-1 downstream of oncogenic KRAS Rob Rottapel, Princess Margaret Cancer Center 9:45 am - 10:00 am A secretory kinase complex regulates extracellular protein phosphorylation Jixin Cui, UCSD 10:00 am - 10:30 am Structural principles of protein kinase regulation Frank Sicheri, Lunenfeld-Tanenbaum Research Institute 10:30 am - 11:00 am Networking and Coffee Break 11:00 am - 11:30 am Regulation of allosteric function of the HER/ErbB receptors Natalia Jura, UCSF 11:30 am - 11:45 am Unorthodox functions of the ancient protein kinase-like UbiB family enable isoprenoid lipid biosynthesis Jonathan Stefely, University of Wisconsin-Madison 11:45 am - 12:00 pm Protein kinase docking systems Eric Weiss, Northwestern University 12:00 pm - 12:30 pm Molecular mechanisms that regulate Raf kinase signaling in normal and disease states Deborah Morrison, National Cancer Institute

6 Monday, December 7, 2015, continued 12:30 pm 2:00 pm Networking Luncheon 2:00 pm 3:00 pm Attendee free time 3:00 pm 5:00 pm Session 6 New Insights Revealed by Structure Chair: Mark Lemmon, University of Pennsylvania 3:00 pm - 3:30 pm Talk tba Stefan Knapp, Oxford University 3:15 pm - 3:45 pm The structure of a toxoplasma cyst wall pseudokinase reveals a scaffold forming an unusual hollow hexamer Michael Reese, UT Southwestern Medical Center 3:45 pm - 4:00 pm Molecular mechanism of CCAAT-Enhancer Binding Protein (C/EBP) recruitment by the TRIB1 pseudokinase Peter Mace, The Walter and Eliza Hall Institute of Medical Research 4:00 pm - 4:15 pm Unravelling a novel kinase-regulated signalling pathway in gastric cancers Isabelle Lucet, The Walter and Eliza Hall Institute of Medical Research 4:15 pm - 4:45 pm Defining juxtamembrane, tyrosine and serine phosphorylation requirements for RET activation and signaling Ivan Plaza-Menacho, Structural Biology Laboratory London Research Institute 4:45 pm - 5:00 pm To be or not to be a pseudokinase tales of two secretory pathway kinases Junyu Xiao, State Key Laboratory of Protein and Plant Gene Research 5:00 pm 7:00 pm Poster Session 7:00 pm - Attendees on own for dinner and free time

7 Tuesday, December 8, :00 am 8:15 am Breakfast 8:30 am 12:45 pm Session 7 Pathogenic Kinases/Pseudokinases as Pharmacological Targets Chair: Tony Hunter, Salk Institute for Biological Studies 8:30 am - 9:30 am Talk tba Dario Alessi, University of Dundee 9:30 am - 9:45 am Investigation of polypharmacology and conformation regulation of RAF kinases Chao Zhang, University of Southern California 9:45 am - 10:00 am Targeting allosteric activation of EGFR Eileen Kennedy, College of Pharmacy, University of Georgia 10:00 am - 10:30 am Targeting Her3 with covalent bifunctional inhibitors Nathanael Gray, Harvard University 10:30 am - 11:00 am Networking and Coffee Break 11:00 am - 11:30 am Kinases as molecular switches: Conserved mechanisms drive oncogenic mutations and deletions Shiva Malek, Genentech, Inc. 11:30 am - 11:45 am Pathogenic effector kinases and pseudokinases: just curiosities or tip of an iceberg? Krzysztof Pawlowski, Warsaw University of Life Sciences 11:45 am - 12:00 pm Reduced kinase activity of DYRK1B mutants found in cancer and metabolic syndrome and kinase independent functions for DYRK1B Simon Cook The Babraham Institute, Babraham Research Campus 12:00 pm - 12:30 pm Talk tba Kevan Shokat, UCSF 12:30 pm - 12:45 pm Best Poster Awards Presentation and Concluding Remarks