Premium
PP1/PP2A phosphatases inhibitors okadaic acid and calyculin A block ERK5 activation by growth factors and oxidative stress
Author(s) -
Garcia Lourdes,
Garcia Fatima,
Llorens Franc,
Unzeta Mercedes,
Itarte Emilio,
Gómez Néstor
Publication year - 2002
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(02)02950-2
Subject(s) - okadaic acid , protein phosphatase 2 , phosphatase , protein kinase c , microbiology and biotechnology , kinase , chemistry , protein kinase a , biology , biochemistry , phosphorylation
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.