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1. Introduction
2. The human kinome
3. PKA sequence
4. PKA and Src define conserved subdomains
5. cAMP is an ancient signaling molecule
6. cAMP dependent protein kinase
7. Outline
8. PKI is a highly specific PKA inhibitor
9. PKI structure
10. Crystallized structure of PKI
11. What do we learn from the sequence of PKI?
12. Cross linked residues at active site
13. N lobe
14. Glycine-rich loop
15. The catalytic machinery (1)
16. The catalytic machinery (2)
17. Prototype for catalysis
18. Conserved active site residues
19. Opening and closing of the active site cleft
20. Close-up on active site
21. Inhibitor peptide docks into active site (1)
22. Inhibitor peptide docks into active site (2)
23. The super family of kinases
24. Correlating secondary structure and sequence
25. Subdomains are conserved
26. What can we learn from the structural kinome?
27. Anatomy of a kinase
28. Analysis of protein kinase core by LSP
29. LSP
30. The assembly of a hydrophobic spine
31. Regulatory spine
32. Second hydrophobic motif - catalytic spine
33. The kinase hydrophobic core
34. F-Helix as a scaffold
35. Insulin receptor kinase
36. PKB and Akt
37. Kinase activation
38. Why is this phosphate so important?
39. Phosphorylation of Thr197
40. Allostery and regulation by phosphorylation in EPK
41. Importance of one phosphate
42. Phosphorylation of activation segment
43. Is phosphorylation of activation loop sufficient?
44. Optimizing the N-lobe for catalysis (1)
45. Protein kinase family members
46. PKA catalytic subunit
47. C-tail
48. The C-tail of PKA
49. Cis regulatory element
50. Optimizing the N-lobe for catalysis (2)
51. Optimizing the N-lobe for catalysis (3)
52. Optimizing the N-lobe for catalysis (4)
53. Priming of the C-lobe and the N-lobe for catalysis
54. Future challenges
55. Questions about inhibition and activation
56. PKA architecture
57. The surface of PKA
58. The regulatory subunits (1)
59. Extended complex interface
60. Conformational dynamics of the regulatory subunit
61. Conformational changes in RI-alpha
62. A-Kinase Anchoring Proteins (AKAPs)
63. Regulation and localization of PKA
64. The regulatory subunits (2)
65. Integration of signaling by PKA
66. Docking domain of RI-alpha bound to DAKAP2
67. PKA proteome
68. PKA signaling
69. Acknowledgements

Topics Covered

• Overview of protein kinase structure and function using PKA as a prototype for this enzyme superfamily
• What we have learned from the overall structural kinome
• Comparison of many protein kinases
• Eukaryotic protein kinase regulation
• Elucidation of general rules of architecture
• Illustration of how PKA is regulated by cAMP and how it is localized to specific macromolecular complexes through scaffold proteins

Links

Series:

• Protein Phosphorylation

Categories:

• Biochemistry

Talk Citation

Taylor, S. (2010, November 30). Protein kinase structure, function and regulation [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved January 27, 2020, from https://hstalks.com/bs/1886/.

Publication History

• Published on November 30, 2010

Financial Disclosures

• Prof. Susan Taylor has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.