PEST motif serine and tyrosine phosphorylation controls vascular endothelial growth factor receptor 2 stability and downregulation

Molecular and Cellular Biology

Volumn 31, Issue 10, 2011, Pages 2010-2025

  Meyer, Rosana D ^a   Srinivasan, Srimathi ^a   Singh, Amrik J ^a   Mahoney, John E ^a   Gharahassanlou, Kobra Rezazadeh ^a   Rahimi, Nader ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP DEPENDENT PROTEIN KINASE; LYSINE; MITOGEN ACTIVATED PROTEIN KINASE KINASE 6; MITOGEN ACTIVATED PROTEIN KINASE P38; SERINE; UBIQUITIN PROTEIN LIGASE E3; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 2;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME INACTIVATION; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; RECEPTOR DOWN REGULATION; REGULATORY MECHANISM; SWINE; UBIQUITINATION;

A KINASE ANCHOR PROTEINS; ANIMALS; BETA-TRANSDUCIN REPEAT-CONTAINING PROTEINS; BLOTTING, WESTERN; CELL LINE; CYCLIC AMP-DEPENDENT PROTEIN KINASES; ENDOTHELIAL CELLS; HUMANS; IMMUNOPRECIPITATION; MAP KINASE KINASE 6; MUTAGENESIS, SITE-DIRECTED; NEOVASCULARIZATION, PHYSIOLOGIC; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHORYLATION; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN STABILITY; RNA, SMALL INTERFERING; SERINE; SIGNAL TRANSDUCTION; SWINE; TYROSINE; UBIQUITINATION; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 79956098305     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.01006-10     Document Type: Article

References (50)

1. Adams, R. H., and K. Alitalo. 2007.Molecular regulation of angiogenesis and lymphangiogenesis. Nat. Rev. Mol. Cell Biol. 8:464-478.
2. Bhattacharya, R. 2005. Regulatory role of dynamin-2 in VEGFR-2/KDR-mediated endothelial signaling. FASEB J. 19:1692-1694.
3. Bruns, A. F. 2010. Ligand-stimulated VEGFR2 signaling is regulated by co-ordinated trafcking and proteolysis. Trafc 11:161-174.
4. Cleaver, O., and D. A. Melton. 2003. Endothelial signaling during development. Nat. Med. 9:661-668.
5. Crusio, K. M., B. King, L. B. Reavie, and I. Aifantis. 2010. The ubiquitous nature of cancer: the role of the SCF(Fbw7) complex in development and transformation. Oncogene 29:4865-4873.
6. Dayanir, V., R. D. Meyer, K. Lashkari, and N. Rahimi. 2002. Identication of tyrosine residues in vascular endothelial growth factor receptor-2/FLK-1 involved in activation of phosphatidylinositol 3-kinase and cell proliferation. J. Biol. Chem. 277:27081-27087.
7. Enslen, H., J. Raingeaud, and R. J. Davis. 1998. Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. J. Biol. Chem. 273:1741-1748.
8. Folkman, J. 2006. Angiogenesis. Annu. Rev. Med. 57:1-18.
9. Gampel, A. 2006. VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment. Blood 108:2624-2631.
10. García-Alai, M. M. 2006. Molecular basis for phosphorylation-dependent, PEST-mediated protein turnover. Structure 14:309-319.
11. Haglund, K., P. P. Di Fiore, and I. Dikic. 2003. Distinct monoubiquitin signals in receptor endocytosis. Trends Biochem. Sci. 28:598-603.
12. Hicke, L. 2001. Protein regulation by monoubiquitin. Nat. Rev. Mol. Cell Biol. 2:195-201.
13. Husain, D., et al. 2010. Role of c-Cbl dependent regulation of phospholipase Cg1 activation in experimental choroidal neovascularization. Investig. Ophthalmol. Vis. Sci. [Epub ahead of print.].
14. Ikeda, S., et al. 2005. Novel role of ARF6 in vascular endothelial growth factor-induced signaling and angiogenesis. Circ. Res. 96:467-475.
15. Issbrücker, K. 2003. p38 MAP kinase-a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability. FASEB J. 17:262-264.
16. Kuida, K., and D. M. Boucher. 2004. Functions of MAP kinases: insights from gene-targeting studies. J. Biochem. 135:653-656.
17. Labrecque, L., I. Royal, D. S. Surprenant, C. Patterson, D. Gingras, and R. Béliveau. 2003. Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol. Mol. Biol. Cell 14:334-347.
18. Lamalice, L., F. Houle, G. Jourdan, and J. Huot. 2004. Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38. Oncogene 23:434-445.
19. Lampugnani, M. G., F. Orsenigo, M. C. Gagliani, C. Tacchetti, and E. Dejana. 2006. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J. Cell Biol. 174:593-604.
20. Lu, Z., and T. Hunter. 2009. Degradation of activated protein kinases by ubiquitination. Annu. Rev. Biochem. 78:435-475.
21. Meyer, R. D., C. Latz, and N. Rahim. 2003. Recruitment and activation of phospholipase Cgamma1 by vascular endothelial growth factor receptor-2 are required for tubulogenesis and differentiation of endothelial cells. J. Biol. Chem. 278:16347-16355.
22. Meyer, R. D., D. B. Sacks, and N. Rahimi. 2008. IQGAP1-dependent signaling pathway regulates endothelial cell proliferation and angiogenesis. PLoS One 3:e3848.
23. Meyer, R. D., D. Husian, and N. Rahimi. 2011. c-Cbl inhibits angiogenesis and tumor growth by suppressing activation of PLCγ1. Oncogene [Epub ahead of print.] doi:10.1038/onc.2010.597.
24. Meyer, R. D., et al. 2004. Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation. Oncogene 23:5523-5531.
25. Mudgett, J. S. 2000. Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proc. Natl. Acad. Sci. U. S. A. 97:10454-10459.
26. Prakash, S., L. Tian, K. S. Ratliff, R. E. Lehotzky, and A. Matouschek. 2004. An unstructured initiation site is required for efcient proteasome-mediated degradation. Nat. Struct. Mol. Biol. 11:830-837.
27. Rahimi, N., T. E. Golde, and R. D. Meyer. 2009. Identication of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells. Cancer Res. 69:2607-2614.
28. Rahimi, N., V. Dayanir, and K. Lashkari. 2000. Receptor chimeras indicate that the vascular endothelial growth factor receptor-1 (VEGFR-1) modulates mitogenic activity of VEGFR-2 in endothelial cells. J. Biol. Chem. 275:16986-16992.
29. Rahimi, N. 2006. VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy. Front. Biosci. 11:818-829.
30. Raingeaud, J., A. J. Whitmarsh, T. Barrettd, B. Dérijar, and R. J. Davis. 1996. MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Mol. Cell. Biol. 16:1247-1255.
31. Ravid, T., and M. Hochstrasser. 2008. Diversity of degradation signals in the ubiquitin-proteasome system. Nat. Rev. Mol. Cell Biol. 9:679-690.
32. Rechsteiner, M., and S. W. Rogers. 1996. PEST sequences and regulation by proteolysis. Trends Biochem. Sci. 21:267-271.
33. Rechsteiner, M. 1990. PEST sequences are signals for rapid intracellular proteolysis. Semin. Cell Biol. 1:433-440.
34. Robidoux, J. 2005. Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes. Mol. Cell. Biol. 25: 5466-5479.
35. Rousseau, S., F. Houle, J. Landry, and J. Huot. 1997. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganization and cell migration in human endothelial cells. Oncogene 15:2169-2177.
36. Sillibourne, J. E., and M. Bornens. 2010. Polo-like kinase 4: the odd one out of the family. Cell Div. 5:25.
37. Singh, A. J., et al. 2007. A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis. Proc. Natl. Acad. Sci. U. S. A. 104:5413-5418.
38. Singh, A. J., R. D. Meyer, H. Band, and N. Rahim. 2005. The carboxyl terminus of VEGFR-2 is required for PKC-mediated down-regulation. Mol. Biol. Cell. 16:2106-2118.
39. Sorkin, A., and M. von Zastrow. 2009. Endocytosis and signalling: intertwining molecular networks. Nat. Rev. Mol. Cell Biol. 10:609-622.
40. Stambolic, V., and J. R. Woodgett. 1994. Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem. J. 303:701-704.
41. Takahashi, T., S. Yamaguchi, K. Chida, and M. A. Shibuya. 2001. Single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J. 20:2768-2778.
42. Taskén, K., and E. M. Aandahl. 2004. Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol. Rev. 84:137-167.
43. Tompa, P., et al. 2004. On the sequential determinants of calpain cleavage. J. Biol. Chem. 279:20775-20785.
44. Uhler, M. D., and G. S. McKnight. 1987. Expression of cDNAs for two isoforms of the catalytic subunit of cAMP-dependent protein kinase. J. Biol. Chem. 262:15202-15207.
45. Ungar, A. R., and R. T. Moon. 1996. Inhibition of protein kinase A phenocopies ectopic expression of hedgehog in the CNS of wild-type and Cyclops mutant embryos. Dev. Biol. 178:186-191.
46. Westphal, R. S. 1999. Regulation of NMDA receptors by an associated phosphatase-kinase signaling complex. Science 285:93-96.
47. Winston, J. T., D. M. Koepp, C. Zhu, S. J. Elledge, and J. W. Harper. 1999. A family of mammalian F-box proteins. Curr. Biol. 9:1180-1182.
48. Wong, W., and J. D. Scott. 2004. AKAP signalling complexes: focal points in space and time. Nat. Rev. Mol. Cell Biol. 5:959-970.
49. Yada, M., et al. 2004. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 23:2116-2125.
50. Zhang, S. 1995. Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J. Biol. Chem. 270:23934-23936.