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

Abstract:

: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 H(2)O(2) as well as in PC12 cells stimulated by nerve growth factor and H(2)O(2). 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Garcia L,Garcia F,Llorens F,Unzeta M,Itarte E,Gómez N

doi

10.1016/s0014-5793(02)02950-2

keywords:

subject

Has Abstract

pub_date

2002-07-17 00:00:00

pages

90-4

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579302029502

journal_volume

523

pub_type

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