Bcl-2 phosphorylation required for anti-apoptosis function
- PMID: 9115213
- DOI: 10.1074/jbc.272.18.11671
Bcl-2 phosphorylation required for anti-apoptosis function
Abstract
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.
Similar articles
-
Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A.J Biol Chem. 1998 Dec 18;273(51):34157-63. doi: 10.1074/jbc.273.51.34157. J Biol Chem. 1998. PMID: 9852076
-
Interleukin-3 and bryostatin-1 mediate hyperphosphorylation of BCL2 alpha in association with suppression of apoptosis.J Biol Chem. 1994 Oct 28;269(43):26865-70. J Biol Chem. 1994. PMID: 7929424
-
A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis.J Biol Chem. 1998 Sep 25;273(39):25436-42. doi: 10.1074/jbc.273.39.25436. J Biol Chem. 1998. PMID: 9738012
-
Novel role for JNK as a stress-activated Bcl2 kinase.J Biol Chem. 2001 Jun 29;276(26):23681-8. doi: 10.1074/jbc.M100279200. Epub 2001 Apr 25. J Biol Chem. 2001. PMID: 11323415
-
Regulation of Bcl2 phosphorylation and potential significance for leukemic cell chemoresistance.J Natl Cancer Inst Monogr. 2001;(28):30-7. doi: 10.1093/oxfordjournals.jncimonographs.a024254. J Natl Cancer Inst Monogr. 2001. PMID: 11158204 Review.
Cited by
-
The phosphorylation-dependent regulation of mitochondrial proteins in stress responses.J Signal Transduct. 2012;2012:931215. doi: 10.1155/2012/931215. Epub 2012 Jul 15. J Signal Transduct. 2012. PMID: 22848813 Free PMC article.
-
A multimeric model for murine anti-apoptotic protein Bcl-2 and structural insights for its regulation by post-translational modification.J Mol Model. 2003 Oct;9(5):298-303. doi: 10.1007/s00894-003-0152-y. Epub 2003 Aug 30. J Mol Model. 2003. PMID: 14517609
-
Infection of macrophage-like THP-1 cells with Mycobacterium avium results in a decrease in their ability to phosphorylate nucleolin.Infect Immun. 2000 Jun;68(6):3121-8. doi: 10.1128/IAI.68.6.3121-3128.2000. Infect Immun. 2000. PMID: 10816453 Free PMC article.
-
Phosphorylation of Bcl-2 and Bax proteins during hypoxia in newborn piglets.Neurochem Res. 2001 Jan;26(1):1-9. doi: 10.1023/a:1007654912421. Neurochem Res. 2001. PMID: 11358275
-
Contribution of Bcl-2 phosphorylation to Bak binding and drug resistance.Cancer Res. 2013 Dec 1;73(23):6998-7008. doi: 10.1158/0008-5472.CAN-13-0940. Epub 2013 Oct 4. Cancer Res. 2013. PMID: 24097825 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
