MAPKAP KINASE-2 IS ACTIVATED BY HEAT-SHOCK AND TNF-ALPHA - IN-VIVO PHOSPHORYLATION OF SMALL HEAT-SHOCK PROTEIN RESULTS FROM STIMULATION OF THE MAP KINASE CASCADE

被引：55

作者：

ENGEL, K ^{[1
]}

AHLERS, A ^{[1
]}

BRACH, MA ^{[1
]}

HERRMANN, F ^{[1
]}

GAESTEL, M ^{[1
]}

机构：

[1] MDC BERLIN BUCH, D-13122 BERLIN, GERMANY

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 1995年 / 57卷 / 02期

关键词：

MITOGEN ACTIVATED PROTEIN KINASES; HEAT SHOCK; TNF-ALPHA; SMALL HEAT-SHOCK PROTEINS;

D O I：

10.1002/jcb.240570216

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：

The activation of MAPKAP kinase 2 was investigated under heat-shock conditions in mouse Ehrlich ascites tumor cells and after treatment of human M07 cells with tumor necrosis factor-alpha (TNF-alpha). MAPKAP kinase 2 activity was determined using the small heat-shock proteins (sHsps) Hsp25 and Hsp27 as substrates. In both cell types, about a threefold increase in MAPKAP kinase 2 activity could be detected in a time interval of about 10-15 min after stimulation either by heat shock or TNF-alpha. Phosphorylation of MAPKAP kinase 2, but not the level of MAPKAP kinase 2 mRNA, was increased after heat shock in EAT cells. It is further shown that activation of MAPKAP kinase 2 in M07 cells is accompanied by increased MAP kinase activity. These data strongly suggest that increased phosphorylation of the sHsps after heat shock or TNF-alpha treatment results from phosphorylation by MAPKAP kinase 2, which itself is activated by phosphorylation through MAP kinases. Hence, we demonstrate that MAPKAP kinase 2 is responsible not only for phosphorylation of sHsps in vitro but also in vivo. The findings link sHsp phosphorylation to the MAP kinase cascade, explaining the early phosphorylation of sHsp that is stimulated by a variety of inducers such as mitogens, phorbol esters, thrombin, calcium ionophores, and heat shock. (C) 1995 Wiley-Liss, Inc.

引用

页码：321 / 330

页数：10

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