title: Phosphorylation of Bcl-2 protein and association with p21Ras in Ras-induced apoptosis.
abstract: p21Ras mediates mitogenic responses and also renders cells susceptible to apoptosis after inhibition of protein kinase C (PKC) activity. Ras-induced apoptosis can be blocked by the proto-oncogene bcl-2, but the biochemical or functional nature of Bcl-2 regulation of Ras-induced apoptosis is not understood. We demonstrate that Bcl-2 and p21Ras molecules can be co-immunoprecipitated in Jurkat cells. The level of this association is enhanced when an apoptotic stimulus (inhibition of PKC activity) is delivered. Bcl-2/p21Ras association is coincident with new phosphorylation of the Bcl-2 protein. Inhibition of this phosphorylation prevents protection from apoptosis by Bcl-2, providing a functional correlation to the phosphorylation event. The Bcl-2/p21Ras association cannot be competed by exogenous glutathione S-transferase-Ras fusion protein, suggesting that the endogenous complex may be formed before cell lysis. These results provide a possible mechanism of regulation of Ras-induced apoptosis by Bcl-2.
authors.affiliation: Cancer Research Center, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.forename: D V
authors.initials: DV
authors.lastname: Faller
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011493:Protein Kinase C; D015689:Oncogene Protein p21(ras)