EXPRESSION OF A CATALYTICALLY INERT SYP BLOCKS ACTIVATION OF MAP KINASE PATHWAY DOWNSTREAM OF P21(RAS)

The precise role of the protein tyrosine phosphatase Syp in insulin signaling is not well understood. We previously reported that expression of catalytically inactive Syp phosphatase blocked stimulation of mitogen-activated protein (MAP) kinase by insulin. In this study, we investigated the effect of dominant negative Syp on the intermediates in MAP kinase pathway. The expression of dominant negative Syp blocked the activation of MEK and raf-1 kinase in response to insulin and had no detectable effect on insulin-induced activation of p21(ras). These data su est that the target of the Syp phosphatase may reside in proteins immediately downstream of p21(ras). (C) 1995 Academic Press, Inc.