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1. Introduction
2. Main messages of the lecture
3. Endocytosis as a signal attenuation process
4. Evolution of the EGFR/ErbB family
5. EGFR function - an example
6. Evolution of negative regulation
7. RTK Signaling as a three act play - a scheme
8. RTK Signaling as a three act play
9. Oncogenic viruses manipulate receptor signaling
10. Prolonged signaling by a poxviral growth factor
11. Viral ligands evade receptor down-regulation
12. EGFR endocytosis in CHO cells
13. Entry routes of animal viruses
14. Clathrin mediated pathway of receptor endocytosis
15. Clathrin independent pathway
16. Major sorting sites and players of EGFR
17. Major sorting sites of EGFR - a scheme
18. Two pathways of receptor endocytosis
19. Sorting of activated receptors at plasma membrane
20. c-CBL
21. Protein ubiquitylation
22. c-CBL role in ubiquitylation of EGFR
23. c-CBL role in degradation of EGFR
24. Regulation of receptor sorting for degradation
25. Mono-Ubiquitin - a reversible sorting signal
26. Mono-Ubiquitin as a location signal in yeast
27. RTK endocytosis
28. The inducible c-CBL docking site at Tyr-1045
29. Y1045F-EGFR is endocytosis defective
30. Y1045F mutation potentiates EGF signaling
31. Endocytosis of EGFR attenuates signaling
32. Signaling en-route to the lysosome
33. Ubiquitylation of receptor tyrosine kinase
34. Endocytosis in the absence of c-CBL or EGF
35. Multi-ubiquitylation drives EGFR degradation
36. Sites for multi-ubiquitylation
37. Mono-ubiquitin-recognizing endocytic machinery
38. Ubiquitin-binding domains
39. Ubiquitylation domains in endocytosis proteins
40. Ubiquitylation of the endocytic machinery
41. Ubiquitin-interacting motif
42. The double action of the UIM of Hgs
43. Dual function of UIM domain
44. Nedd4 is the E3 ligase associated with the UIM
45. Potential functions of UIMs
46. Alternative model
47. The journey to the lysosome: sorting at the MVB
48. Fusion of MVBs with lysosomes
49. Receptor sorting at the MVB
50. MVB sorting at Tsg101
51. The role of Tsg101 and ESCRTs
52. Tal regulates sorting at MVB
53. Tal enables cargo reloading by Tsg102
54. Protein networks at the sorting steps of RTKs
55. Antibody induced endocytosis of RTK
56. Synergistical effect of mAbs
57. Model for antibody induced endocytosis of RTK
58. Antibody-drug internalization
59. Protein kinase C induces receptor recycling
60. RTK endocytosis regulates cell migration in flies
61. RTK endocytosis in cancer 1
62. RTK endocytosis in cancer 2
63. Acknowledgements

Topics Covered

• Signal transduction by growth factor-activated protein tyrosine kinase receptors
• Receptor endocytosis
• The three vesicular sorting steps occurring at the plasma membrane, in endosomes and in a pre-lysosomal compartment
• The emerging role of mono-ubiquitin and ubiquitin-binding proteins in sorting of active receptors to degradation

Links

Series:

• Signal Transduction via Protein Tyrosine Kinase Receptors

Categories:

• Cell Biology

Talk Citation

Yarden, Y. (2007, October 1). Negative regulation of RTKs: receptor ubiquitylation, endocytosis and feedback loops [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 15, 2025, from https://doi.org/10.69645/ODIQ2543.
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Publication History

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

Financial Disclosures

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