Pim-1激酶通过在促凋亡蛋白Bad的Ser112守门位点使其磷酸化，促进其失活。
Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site.
作者信息
Aho Teija L T, Sandholm Jouko, Peltola Katriina J, Mankonen Harri P, Lilly Michael, Koskinen Päivi J
机构信息
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Tykistökatu 6 B, 20520 Turku, Finland.
出版信息
FEBS Lett. 2004 Jul 30;571(1-3):43-9. doi: 10.1016/j.febslet.2004.06.050.
Constitutive expression of the Pim-1 kinase prolongs survival of cytokine-deprived FDCP1 cells, partly via maintenance of Bcl-2 expression. Here, we show that Pim-1 colocalizes and physically interacts with the pro-apoptotic Bad protein and phosphorylates it in vitro on serine 112, which is a gatekeeper site for its inactivation. Furthermore, wild-type Pim-1, but not a kinase-deficient mutant, enhances phosphorylation of this site in FDCP1 cells and protects cells from the pro-apoptotic effects of Bad. Our results suggest that phosphorylation of Bad by Pim-1 is one of several mechanisms via which the Pim-1 kinase can enhance Bcl-2 activity and promote cell survival.
Pim-1激酶的组成型表达可延长细胞因子剥夺的FDCP1细胞的存活时间，部分原因是通过维持Bcl-2的表达。在此，我们表明Pim-1与促凋亡蛋白Bad共定位并发生物理相互作用，并在体外将其丝氨酸112位点磷酸化，该位点是其失活的关键位点。此外，野生型Pim-1而非激酶缺陷型突变体可增强FDCP1细胞中该位点的磷酸化，并保护细胞免受Bad的促凋亡作用。我们的结果表明，Pim-1对Bad的磷酸化是Pim-1激酶增强Bcl-2活性并促进细胞存活的几种机制之一。
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