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1. Introduction
2. Receptor tyrosine kinase family
3. IR activation and downstream recruitment
4. Protein recruitment: mechanism and specificity
5. Canonical (monomeric) Src SH2 domain structure
6. Structure of the insulin receptor kinase (IRK)
7. Structural transition from IRK-0P to IRK-3P
8. Dynamic state of activation loop
9. Specificity for Tyr and Met as substrates
10. Tyrosine kinase autoinhibition modes
11. IRK activation loop: a SH2 recruitment site
12. Lnk family of adapter proteins
13. Crystals of APS SH2 domain
14. Crystal structure of the APS SH2 domain (1)
15. Crystal structure of the APS SH2 domain (2)
16. Gel filtration studies of APS(SH2) /SH2-B(SH2)
17. Functional role for the APS SH2 dimer
18. Turn-containing IRK-3P activation loop
19. Crystals of APS(SH2):IRK-3P complex
20. Crystal structure of APS(SH2): IRK complex
21. Twin p-Tyr recognition in the IRK A-loop
22. APS recruitment and phosphorylation by the IR
23. Grb7/10/14 family
24. Sequence alignment of BPS region in Grb-s
25. Inhibition of IRK catalytic activity
26. Crystals of Grb14(BPS): IRK-3P complex
27. Interaction of Grb14 BPS with IRK (1)
28. Interaction of Grb14 BPS with IRK (2)
29. Interaction of Grb14 BPS with IRK (3)
30. Co-IP of Grb14 BPS mutants with IR
31. BPS Region of Grb14 versus Grb7
32. Crystal structure of the Grb10 SH2 domain (1)
33. Crystal structure of the Grb10 SH2 domain (2)
34. Grb10 is a dimer in solution
35. Steric block to P+3 binding (1)
36. Steric block to P+3 binding (2)
37. Preference for turn-containing pTyr sequences
38. Grb14 SH2 dimer
39. Model of Grb14 BPS-SH2 interaction with IRK
40. Importance of SH2 for Grb14 binding to the IR
41. Grb14 Interaction with IR (1)
42. Grb14 Interaction with IR (2)
43. Grb14 Interaction with IR (3)
44. Summary (1)
45. Summary (2)
46. 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:

• Signal Transduction via Protein Tyrosine Kinase Receptors

Categories:

• Biochemistry
• Metabolism & Nutrition

Therapeutic Areas:

• Cardiovascular & Metabolic

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 20, 2024, from https://hstalks.com/bs/454/.
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Publication History

• Published on October 1, 2007
• Archived on May 31, 2018

Financial Disclosures

• Dr. Stevan Hubbard has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.