PP1/PP2A phosphatases inhibitors okadaic acid and calyculin A block ERK5 activation by growth factors and oxidative stress

被引：45

作者：

Garcia, L ^{[1
]}

Garcia, F ^{[1
]}

Llorens, F ^{[1
]}

Unzeta, M ^{[1
]}

Itarte, E ^{[1
]}

Gómez, N ^{[1
]}

机构：

[1] Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain

来源：

FEBS LETTERS | 2002年 / 523卷 / 1-3期

关键词：

extracellular signal-regulated protein kinase 5 okadaic acid; calyculin A; protein kinase C; epidermal growth factor;

D O I：

10.1016/S0014-5793(02)02950-2

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：

Okadaic acid is an inhibitor of the protein Ser/Thr phosphatases PP1 and PP2A, which blocks the activation of extracellular signal-regulated protein kinase 5 (ERK5), a member of the MAP kinase family activated by growth factors and several types of stressors. The blocking of ERK5 activation by okadaic acid was observed in HeLa cells exposed to epidermal growth factor and H2O2 as well as in PC12 cells stimulated by nerve growth factor and H2O2. Calyculin A, another PP1 and PP2A inhibitor, behaved similarly although these compounds are not structurally related. This suggests that either PP1 or PP2A or both are necessary for ERK5 activation. Protein kinase C (PKC) acts as a negative regulator of the ERK5 activation pathway, however our data suggest that the effects of PKC and the phosphatase are unrelated. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：90 / 94

页数：5

共 16 条

[1] c-Src is required for oxidative stress-mediated activation of big mitogen-activated protein kinase 1 (BMK1) [J].

Abe, J ;

Takahashi, M ;

Ishida, M ;

Lee, JD ;

Berk, BC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20389-20394

[2] INACTIVATION OF P42 MAP KINASE BY PROTEIN PHOSPHATASE 2A AND A PROTEIN-TYROSINE-PHOSPHATASE, BUT NOT CL100, IN VARIOUS CELL-LINES [J].

ALESSI, DR ;

GOMEZ, N ;

MOORHEAD, C ;

LEWIS, T ;

KEYSE, SM ;

COHEN, P .

CURRENT BIOLOGY, 1995, 5 (03) :283-295

[3] Okadaic acid and anisomycin are protective and stimulate the SAP/JNK pathway [J].

Barancik, M ;

Htun, P ;

Schaper, W .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1999, 34 (02) :182-190

[4]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[5] MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway [J].

Chao, TH ;

Hayashi, M ;

Tapping, RI ;

Kato, Y ;

Lee, JD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (51) :36035-36038

[6] Multiple mitogen-activated protein kinase signaling pathways connect the Cot oncoprotein to the c-jun promoter and to cellular transformation [J].

Chiariello, M ;

Marinissen, MJ ;

Gutkind, JS .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (05) :1747-1758

[7] Granulocyte colony-stimulating factor induces Erk5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C - Regulation of cell proliferation and survival [J].

Dong, F ;

Gutkind, JS ;

Larner, AC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (14) :10811-10816

[8] ISOLATION OF MEK5 AND DIFFERENTIAL EXPRESSION OF ALTERNATIVELY SPLICED FORMS [J].

ENGLISH, JM ;

VANDERBILT, CA ;

XU, SC ;

MARCUS, S ;

COBB, MH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (48) :28897-28902

[9]

GAUSE KC, 1993, J BIOL CHEM, V268, P16124

[10] DISSECTION OF THE PROTEIN-KINASE CASCADE BY WHICH NERVE GROWTH-FACTOR ACTIVATES MAP KINASES [J].

GOMEZ, N ;

COHEN, P .

NATURE, 1991, 353 (6340) :170-173

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