PERVANADATE-TRIGGERED MAP KINASE ACTIVATION AND CELL-PROLIFERATION ARE NOT SENSITIVE TO PD-98059 - EVIDENCE FOR STIMULUS-DEPENDENT DIFFERENTIAL PD-98059 INHIBITION-MECHANISM

A tight and stable complex with corresponding protein kinases and phos phatases establishes coupling between activators and inactivators, One such example is emerging from the studies of the Ras-dependent MAP ki nase cascade signaling pathway, Pervanadate, a potent inhibitor of pro tein tyrosine phosphatase, stimulates MAP kinase and elicits cell prol iferation in cultured mouse fibroblasts which is insensitive to PD 980 59, the major inhibitor of upstream MEK, whereas serum- or TPA-trigger ed proliferation is sensitive to PD 98059, It is suggested that imbala nced coordination between protein kinase and protein phosphatase deter mines the cellular responses such as cell proliferation. The PD 98059- insensitive cell proliferation upon protein tyrosine phosphatase inhib ition is attributed to a MEK bypass pathway. (C) 1998 Federation of Eu ropean Biochemical Societies.