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Bcl-2 Phosphorylation Required for Anti-apoptosis Function
Open accessAbstract
The protooncogene Bcl-2 functions as a suppressor of apoptosis in growth factor-dependent cells, but a post-receptor signaling mechanism is not known. We recently reported that interleukin 3 (IL-3) and erythropoietin, or the protein kinase C activator bryostatin-1 (Bryo), not only suppresses apoptosis but also stimulates the phosphorylation of Bcl-2 (May, W. S., Tyler, P. G., Ito, T., Armstrong, D. K., Qatsha, K. A., and Davidson, N. E. (1994) J. Biol. Chem. 269, 26865-26870). To test whether phosphorylation is required for Bcl-2 function, conservative serine --> alanine mutations were produced at the seven putative protein kinase C phosphorylation sites in Bcl-2. Results indicate that the S70A Bcl-2 mutant fails to be phosphorylated after IL-3 or Bryo stimulation and is unable to support prolonged cell survival either upon IL-3 deprivation or etoposide treatment when compared with wild-type Bcl-2. In contrast, a Ser --> Glu mutant, S70E, which may mimic a potential phosphate charge, more potently suppressed the etoposide-induced apoptosis than wild type in the absence of IL-3. Since the loss of function S70A mutant can heterodimerize with its partner protein and death effector Bax, these findings demonstrate that Bcl-2:Bax heterodimerization is not sufficient and Bcl-2 phosphorylation is required for full Bcl-2 death suppressor signaling activity.
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Metadata
- Authors
- Ito, T., Deng, X., Carr, B., & May, W. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 272
- Issue
- 18
- Pages
- 11671-11673
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1970834072
- Cited by
- 541
- References
- 1
- FWCI
- 14.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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