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Publication : BAD Ser128 is not phosphorylated by c-Jun NH2-terminal kinase for promoting apoptosis.

First Author  Zhang J Year  2005
Journal  Cancer Res Volume  65
Issue  18 Pages  8372-8
PubMed ID  16166315 Mgi Jnum  J:101612
Mgi Id  MGI:3604319 Doi  10.1158/0008-5472.CAN-05-0576
Citation  Zhang J, et al. (2005) BAD Ser128 is not phosphorylated by c-Jun NH2-terminal kinase for promoting apoptosis. Cancer Res 65(18):8372-8
abstractText  The phosphorylation and regulation of the proapoptotic Bcl-2 family protein BAD by c-Jun NH2-terminal kinase (JNK) is controversial. JNK can suppress interleukin-3 withdrawal-induced apoptosis via phosphorylation of BAD at Thr201. However, it has also been reported that JNK promotes apoptosis through phosphorylation of BAD at Ser128. Here, we report that JNK is not a BAD Ser128 kinase. JNK phosphorylates murine BAD (mBAD), but not human BAD (hBAD), in which Ser91 is equivalent to Ser128 in mBAD. In contrast, Cdc2, which phosphorylates Ser128, phosphorylates both mBAD and hBAD. Replacement of Ser128 by alanine has no effects on BAD phosphorylation by JNK in vitro and in vivo. Two-dimensional phosphopeptide mapping in combination with phosphoamino acid analysis reveals that JNK does not phosphorylate BAD at Ser128. Elimination of Ser128 phosphorylation has no effects on the proapoptotic activity of BAD in apoptosis induced by UV via JNK or growth factor withdrawal. Thus, our results show that Ser128 is not phosphorylated by JNK for promoting cell death.
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