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

FEBS Letters

Unzeta, Mercedes¹  Itarte, Emilio¹  Garcia, Fatima¹  Garcia, Lourdes¹  Gómez, Néstor¹  Llorens, Franc¹ 

[1] Departament de Bioquı́mica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

关键词: Extracellular signal-regulated protein kinase 5;    Okadaic acid;    Calyculin A;    Protein kinase C;    Epidermal growth factor;    EGF;    epidermal growth factor;    ERK1/2;    extracellular signal-regulated protein kinases 1/2;    ERK5 extracellular signal-regulated protein kinase 5;    FBS;    foetal bovine serum;    NGF;    nerve growth factor;    PC12;    rat pheochromocytoma cell line;    PKC;    protein kinase C;    PP1;    protein phosphatase 1;    PP2A;    protein phosphatase 2A;   

DOI  :  10.1016/S0014-5793(02)02950-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown