Pim-1 kinase promotes inactivation of the pro-apoptotic bad protein by phosphorylating it on the Ser112 gatekeeper site

被引：291

作者：

Aho, TLT

Sandholm, J

Peltola, KJ

Mankonen, HP

Lilly, M

Koskinen, PJ

机构：

[1] Turku Univ, Abo Akad Univ, Turku Ctr Biotechnol, Turku 20520, Finland

[2] Loma Linda Univ, Sch Med, Ctr Mol Biol & Gene Therapy, Loma Linda, CA 92354 USA

[3] Turku Grad Sch Biomed Sci, Turku, Finland

来源：

FEBS LETTERS | 2004年 / 571卷 / 1-3期

基金：

芬兰科学院;

关键词：

Pim-1; kinase; Bcl-2; bad; apoptosis; myeloid cells;

D O I：

10.1016/j.febslet.2004.06.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：43 / 49

页数：7

共 31 条

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