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- Function of important examples of PTK receptor families
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1. The molecular basis of insulin action
- Prof. Morris White
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2. The Eph receptor family
- Prof. Elena Pasquale
- Structure of PTK receptors and regulation of their kinases
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3. EGF receptor family: targets for improving cancer therapy
- Prof. Tony Burgess
- Intracellular signal transduction by PTK receptors
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4. PI 3-kinases and lipid messengers
- Prof. Bart Vanhaesebroeck
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5. RTKs activate the ERK 1/2 MAPK cascade
- Prof. Melanie H. Cobb
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6. The ERK1/2 MAPK cascade
- Prof. Melanie H. Cobb
- Archived Lectures *These may not cover the latest advances in the field
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7. Receptor tyrosine kinases - function, families and evolution
- Prof. Tony Hunter
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9. How the PDGF receptor induces cell proliferation
- Dr. Andrius Kazlauskas
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10. VEGF inhibitors for anti-angiogenic therapy
- Prof. Kari Alitalo
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12. Activation of PTK receptors in solid human tumors
- Dr. Marco Pierotti
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14. SH2-containing PTPs (Shps) in RTK signaling and disease
- Prof. Benjamin G. Neel
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16. Phospholipase C Gamma
- Prof. Graham Carpenter
- Ms. Cornelia Crooke
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17. Imatinib as a paradigm of targeted cancer therapies
- Prof. Brian Druker
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18. EGFR targeted therapies in lung cancer
- Dr. Pasi Janne
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19. The VEGF family
- Prof. Kari Alitalo
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20. The HGF receptor, a targettable regulator of invasive growth
- Prof. Paolo Comoglio
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21. Structural biology of FGF signaling in human development and disease
- Dr. Moosa Mohammadi
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22. EGF receptor family: targets for cancer therapeutics
- Prof. Tony Burgess
Printable Handouts
Navigable Slide Index
- Introduction
- Receptor tyrosine kinase family
- IR activation and downstream recruitment
- Protein recruitment: mechanism and specificity
- Canonical (monomeric) Src SH2 domain structure
- Structure of the insulin receptor kinase (IRK)
- Structural transition from IRK-0P to IRK-3P
- Dynamic state of activation loop
- Specificity for Tyr and Met as substrates
- Tyrosine kinase autoinhibition modes
- IRK activation loop: a SH2 recruitment site
- Lnk family of adapter proteins
- Crystals of APS SH2 domain
- Crystal structure of the APS SH2 domain (1)
- Crystal structure of the APS SH2 domain (2)
- Gel filtration studies of APS(SH2) /SH2-B(SH2)
- Functional role for the APS SH2 dimer
- Turn-containing IRK-3P activation loop
- Crystals of APS(SH2):IRK-3P complex
- Crystal structure of APS(SH2): IRK complex
- Twin p-Tyr recognition in the IRK A-loop
- APS recruitment and phosphorylation by the IR
- Grb7/10/14 family
- Sequence alignment of BPS region in Grb-s
- Inhibition of IRK catalytic activity
- Crystals of Grb14(BPS): IRK-3P complex
- Interaction of Grb14 BPS with IRK (1)
- Interaction of Grb14 BPS with IRK (2)
- Interaction of Grb14 BPS with IRK (3)
- Co-IP of Grb14 BPS mutants with IR
- BPS Region of Grb14 versus Grb7
- Crystal structure of the Grb10 SH2 domain (1)
- Crystal structure of the Grb10 SH2 domain (2)
- Grb10 is a dimer in solution
- Steric block to P+3 binding (1)
- Steric block to P+3 binding (2)
- Preference for turn-containing pTyr sequences
- Grb14 SH2 dimer
- Model of Grb14 BPS-SH2 interaction with IRK
- Importance of SH2 for Grb14 binding to the IR
- Grb14 Interaction with IR (1)
- Grb14 Interaction with IR (2)
- Grb14 Interaction with IR (3)
- Summary (1)
- Summary (2)
- Acknowledgments
Topics Covered
- Introduction to receptor tyrosine kinases (RTKs)
- general mechanisms of protein recruitment to RTKs
- Structure of the insulin receptor tyrosine kinase domain (IRK)
- Autoinhibitory mechanisms in RTKs
- Structure of the Src homology-2 (SH2) domain of APS
- Structure of the APS SH2 domain bound to IRK
- Inhibition of IRK activity by Grb14
- Structure of the Grb14 BPS region bound to IRK
- Structure of the Grb14 SH2 domain
- Model of the interaction between Grb14 and the insulin receptor
Links
Series:
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Talk Citation
Hubbard, S. (2007, October 1). Structure and mechanism of the tyrosine kinase domain of the insulin receptor [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 27, 2024, from https://hstalks.com/bs/454/.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Stevan Hubbard has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Structure and mechanism of the tyrosine kinase domain of the insulin receptor
A selection of talks on Metabolism & Nutrition
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