P21-activated kinase 1 (Pak1) phosphorylates BAD directly at serine 111 in vitro and indirectly through Raf-1 at serine 112

PLoS ONE

Volumn 6, Issue 11, 2011, Pages

  Ye, Diana Z ^a   Jin, Shenghao ^a   Zhuo, Ya ^a   Field, Jeffrey ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

P21 ACTIVATED KINASE 1; PROTEIN BAD; RAF PROTEIN; SERINE; P21 ACTIVATED KINASE;

ARTICLE; BINDING AFFINITY; BINDING SITE; CELL STRAIN HEK293; CONTROLLED STUDY; IN VITRO STUDY; MUTATIONAL ANALYSIS; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; CELL LINE; HUMAN; IMMUNOBLOTTING; IMMUNOPRECIPITATION; METABOLISM; PHOSPHORYLATION; PROTEIN BINDING;

BCL-ASSOCIATED DEATH PROTEIN; CELL LINE; HUMANS; IMMUNOBLOTTING; IMMUNOPRECIPITATION; P21-ACTIVATED KINASES; PHOSPHORYLATION; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-RAF; SERINE;

EID: 80855156758     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0027637     Document Type: Article

References (49)

1. Vander Heiden MG, Thompson CB, (1999) Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis? Nat Cell Biol 1: 209-216.
2. Zha JH, Harada H, Yang E, Jockel J, Korsmeyer SJ, (1996) Serine phosphorylation of death agonist Bad in response to survival factor results in binding to 14-3-3 not Bcl-xL. Cell 87: 619-628.
3. Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR, (2010) The BCL-2 family reunion. Mol Cell 37: 299-310.
4. Datta SR, Dudek H, Tao X, Master S, Fu H, et al. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91: 231-241.
5. Harada H, Becknell B, Wilm M, Mann M, Huang L, et al. (1999) Phosphorylation and Inactivaion of BAD by Mitochondria-Anchored Protein Kinase A. Molecular Cell 3: 413-422.
6. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, et al. (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms. Science 286: 1358-1362.
7. Lizcano JM, Morrice N, Cohen P, (2000) Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155. Biochem J 349: 547-557.
8. Tan Y, Demeter MR, Ruan H, Comb MJ, (2000) BAD Ser-155 phosphorylation regulates BAD/Bcl-XL interaction and cell survival. J Biol Chem 275: 25865-25869.
9. Konishi Y, Lehtinen M, Donovan N, Bonni A, (2002) Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. Mol Cell 9: 1005-1016.
10. Donovan N, Becker EB, Konishi Y, Bonni A, (2002) JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J Biol Chem 277: 40944-40949.
11. Yu C, Minemoto Y, Zhang J, Liu J, Tang F, et al. (2004) JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family protein BAD. Mol Cell 13: 329-340.
12. Wang H, Rapp U, Reed JC, (1996) Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell 87: 629-638.
13. von Gise A, Lorenz P, Wellbrock C, Hemmings B, Berberich-Siebelt F, et al. (2001) Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals. Mol Cell Biol 21: 2324-2336.
14. Hindley A, Kolch W, (2002) Extracellular signal regulated kinase (ERK)/mitogen activated protein kinase (MAPK)-independent functions of Raf kinases. J Cell Sci 115: 1575-1581.
15. Jin S, Zhuo Y, Guo W, Field J, (2005) PAK1-dependent phosphorylation of RAF-1 regulates its mitochondrial localization, phosphorylation of BAD, and BCL-2 association. J Biol Chem 280: 24698-24705.
16. Polzien L, Baljuls A, Rennefahrt UEE, Fischer A, Schmitz W, et al. (2009) Identification of Novel in Vivo Phosphorylation Sites of the Human Proapoptotic Protein BAD. Journal of Biological Chemistry 284: 28004-28020.
17. Manser E, Leung T, Salihuddin H, Zhao Z-S, Lim L, (1994) A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367: 40-46.
18. Bokoch GM, (2003) Biology of the p21-activated kinases. Annu Rev Biochem 72: 743-781.
19. Hofmann C, Shepelev M, Chernoff J, (2004) The genetics of Pak. J Cell Sci 117: 4343-4354.
20. Kumar R, Gururaj AE, Barnes CJ, (2006) p21-activated kinases in cancer. Nat Rev Cancer 6: 459-471.
21. Menard RE, Jovanovski AP, Mattingly RR, (2005) Active p21-activated kinase 1 rescues MCF10A breast epithelial cells from undergoing anoikis. Neoplasia 7: 638-645.
22. Dummler B, Ohshiro K, Kumar R, Field J, (2009) Pak protein kinases and their role in cancer. Cancer Metastasis Rev 28: 51-63.
23. Tang Y, Zhou H, Chen A, Pittman RN, Field J, (2000) The Akt proto-oncogene links Ras to Pak and cell survival signals. J Biol Chem 275: 9106-9109.
24. Schurmann A, Mooney AF, Sanders LC, Sells MA, Wang H-G, et al. (2000) p21-activated kinase (PAK1) phosphorylates the death agonist Bad and protects cells from apoptosis. Mol Cell Biol 20: 453-461.
25. Jakobi R, Moertl E, Koeppel MA, (2001) p21-activated protein kinase γ-PAK suppresses programmed cell death of BALB3T3 fibroblasts. J Biol Chem 276: 16624-16634.
26. Gnesutta N, Qu J, Minden A, (2001) The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis. J Biol Chem 276: 14414-14419.
27. Cotteret S, Jaffer ZM, Beeser A, Chernoff J, (2003) p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD. Mol Cell Biol 23: 5526-5539.
28. Murray BW, Guo C, Piraino J, Westwick JK, Zhang C, et al. (2010) Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth. Proceedings of the National Academy of Sciences 107: 9446-9451.
29. Alavi A, Hood JD, Frausto R, Stupack DG, Cheresh DA, (2003) Role of Raf in vascular protection from distinct apoptotic stimuli. Science 301: 94-96.
30. Wu X, Carr HS, Dan I, Ruvolo PP, Frost JA, (2008) p21 activated kinase 5 activates Raf-1 and targets it to mitochondria. J Cell Biochem 105: 167-175.
31. Tang Y, Yu J, Field J, (1999) Signals from the Ras, Rac and Rho GTPases converge on the Pak protein kinase in Rat-1 fibroblasts. Mol Cell Biol 19: 1881-1891.
32. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, et al. (2000) 14-3-3 Proteins and Survival Kinases Cooperate to Inactivate BAD by BH3 Domain Phosphorylation. Molecular Cell 6: 41-51.
33. Masters SC, Yang H, Datta SR, Greenberg ME, Fu H, (2001) 14-3-3 inhibits Bad-induced cell death through interaction with serine-136. Mol Pharmacol 60: 1325-1331.
34. Tang Y, Marwaha S, Rutkowski JL, Tennekoon GI, Phillips PC, et al. (1998) A role for Pak protein kinases in Schwann cell transformation. Proc Natl Acad Sci USA 95: 5139-5144.
35. Deacon SW, Beeser A, Fukui JA, Rennefahrt UEE, Myers C, et al. (2008) An Isoform-Selective, Small-Molecule Inhibitor Targets the Autoregulatory Mechanism of p21-Activated Kinase. Chemistry & Biology 15: 322-331.
36. Zhang B, Zhang Y, Shacter E, (2004) Rac1 inhibits apoptosis in human lymphoma cells by stimulating Bad phosphorylation on Ser-75. Mol Cell Biol 24: 6205-6214.
37. Obenauer JC, Cantley LC, Yaffe MB, (2003) Scansite 2.0: proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucl Acids Res 31: 3635-3641.
38. Rennefahrt UEE, Deacon SW, Parker SA, Devarajan K, Beeser A, et al. (2007) Specificity Profiling of Pak Kinases Allows Identification of Novel Phosphorylation Sites. J Biol Chem 282: 15667-15678.
39. Peter VH, Indy C, Jon MK, Elzbieta S, Bin Z, (2004) PhosphoSite: A bioinformatics resource dedicated to physiological protein phosphorylation. PROTEOMICS 4: 1551-1561.
40. Wojnowski L, Zimmer AM, Beck TW, Hahn H, Bernal R, et al. (1997) Endothelial apoptosis in Braf-deficient mice. Nat Genet 16: 293-297.
41. Mikula M, Schreiber M, Husak Z, Kucerova L, Ruth J, et al. (2001) Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. Embo J 20: 1952-1962.
42. Huser M, Luckett J, Chiloeches A, Mercer K, Iwobi M, et al. (2001) MEK kinase activity is not necessary for Raf-1 function. Embo J 20: 1940-1951.
43. Baccarini M, (2002) An old kinase on a new path: Raf and apoptosis. Cell Death Differ 9: 783-785.
44. Troppmair J, Rapp UR, (2003) Raf and the road to cell survival: a tale of bad spells, ring bearers and detours. Biochem Pharmacol 66: 1341-1345.
45. Giroux S, Tremblay M, Bernard D, Cardin-Girard JF, Aubry S, et al. (1999) Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Curr Biol 9: 369-372.
46. Cichowski K, Janne PA, (2010) Drug discovery: inhibitors that activate. Nature 464: 358-359.
47. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N, (2010) RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 464: 427-430.
48. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, et al. (2010) RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464: 431-435.
49. Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, et al. (2010) Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. Cell 140: 209-221.