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PMID:11717309
| Citation |
Dramsi, S, Scheid, MP, Maiti, A, Hojabrpour, P, Chen, X, Schubert, K, Goodlett, DR, Aebersold, R and Duronio, V (2002) Identification of a novel phosphorylation site, Ser-170, as a regulator of bad pro-apoptotic activity. J. Biol. Chem. 277:6399-405 |
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| Abstract |
Bad is a pro-apoptotic member of the Bcl-2 family of proteins that is thought to exert a death-promoting effect by heterodimerization with Bcl-X(L), nullifying its anti-apoptotic activity. Growth factors may promote cell survival at least partially through phosphorylation of Bad at one or more of Ser-112, -136, or -155. Our previous work showed that Bad is also phosphorylated in response to cytokines at another site, which we now identify as Ser-170. The functional role of this novel phosphorylation site was assessed by site-directed mutagenesis and analysis of the pro-apoptotic function of Bad in transiently transfected HEK293 and COS-7 cells or by stable expression in the cytokine-dependent cell line, MC/9. In general, mutation of Ser-170 to Ala results in a protein with increased ability to induce apoptosis, similar to the S112A mutant. Mutation of Ser-170 to Asp, mimicking a constitutively phosphorylated site, results in a protein that is virtually unable to induce apoptosis. Similarly, the S112A/S170D double mutant does not cause apoptosis in HEK293 and MC/9 cell lines. These data strongly suggest that phosphorylation of Bad at Ser-170 is a critical event in blocking the pro-apoptotic activity of Bad. |
| Links |
PubMed Online version:10.1074/jbc.M109990200 |
| Keywords |
Amino Acid Substitution; Animals; Apoptosis/physiology; COS Cells; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Cercopithecus aethiops; Cloning, Molecular; Escherichia coli/genetics; Genes, bcl-2; Humans; Mice; Mutagenesis, Site-Directed; Phosphorylation; Phosphoserine/metabolism; Poly(ADP-ribose) Polymerases/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Serine; Transfection; bcl-Associated Death Protein; bcl-X Protein |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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See also
References
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