Expression of a catalytically inert Syp blocks activation of MAP kinase pathway downstream of p21ras.
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 p21ras. These data suggest that the target of the Syp phosphatase may reside in proteins immediately downstream of p21ras.
Sawada
T
T
Department of Signal Transduction, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
Milarski
K L
KL
Saltiel
A R
AR
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002999:Clone Cells; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D016296:Mutagenesis; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D011494:Protein Kinases; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)