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Use of a drug‐resistant mutant of stress‐activated protein kinase 2a/p38 to validate the in vivo specificity of SB 203580
Author(s) -
Eyers Patrick A.,
van den IJssel Paul,
Quinlan Roy A.,
Goedert Michel,
Cohen Philip
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00552-9
Subject(s) - protein kinase a , ask1 , c raf , microbiology and biotechnology , mitogen activated protein kinase kinase , map kinase kinase kinase , p38 mitogen activated protein kinases , map2k7 , protein kinase r , cyclin dependent kinase 2 , mitogen activated protein kinase , chemistry , kinase , biology
Stress‐activated protein kinase 2a, also called p38, is inhibited by SB 203580 and this drug has been used widely to implicate this enzyme in the regulation of many physiological processes. Here, we introduce a novel method of general application, which can be used to establish whether the effects of SB 203580 are mediated via inhibition of stress‐activated protein kinase 2a/p38 or whether they result from ‘non‐specific’ effects. Four events thought to occur upon activation of stress‐activated protein kinase 2a/p38 have been established unequivocally. These are the activation of mitogen‐activated protein kinase‐activated protein kinase‐2 and mitogen‐ and stress‐activated protein kinase‐1 and the phosphorylation of their presumed substrates, heat shock protein 27 and the transcription factor cyclic AMP response element binding protein, respectively. In contrast, the SB 203580‐induced activation of c‐Raf is independent of stress‐activated protein kinase 2a/p38 inhibition.