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Effect of phosphotyrosyl‐IRS‐1 level and insulin receptor tyrosine kinase activity on insulin‐stimulated phosphatidylinositol 3, MAP, and S6 kinase activities
Author(s) -
Wilden Peter A.,
Broadway Dale E.
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041630103
Subject(s) - autophosphorylation , insulin receptor , irs2 , insulin receptor substrate , insulin , endocrinology , tyrosine phosphorylation , medicine , tyrosine kinase , receptor tyrosine kinase , biology , kinase , chemistry , insulin resistance , biochemistry , signal transduction , protein kinase a
The role of tyrosine phosphorylation of the insulin receptor substrate 1 (IRS‐1) was studied utilizing parental CHO cells or CHO cells that overexpress IRS‐1, the insulin receptor, or both IRS‐1 and the insulin receptor. Insulin stimulation of these four cell lines led to progressive levels of IRS‐1 tyrosine phosphorylation of one, two, four, and tenfold. Maximal insulin‐stimulated IRS‐1 associated Ptdlns 3′‐kinase activit in these cells was 1‐, 1.5‐, 3‐, and 3‐fold, while insulin sensitivity, as determined by ED 50 , was 1‐, 2.5‐, 10‐, and 10‐fold. Both sensitivity and maximal response paralleled the increased level of phosphotyrosyl‐IRS‐1; however, the increased level of phosphotyrosyl‐IRS‐1 seen in CHO/IR/IRS‐1 cells did not further increase these responses. Likewise, maximal insulin‐stimulated MAP kinase activity in these cell lines increased in parallel with IRS‐1 tyrosine phosphorylation except in the CHO/IR/IRS‐1 cell lines with activity levels of one‐, five‐, nine‐, and ninefold. However, insulin sensitivity of the MAP and S6 kinases and maximal insulin‐stimulated S6 kinase activity was not changed by a twofold increase in phosphotyrosyl‐IRS‐1, but an increase was observed with insulin‐stimulated receptor autophosphorylation and kinase activity in CHO/IR cells which led to a tenfold increase in insulin receptor autophosphorylation and a fourfold increase in IRS‐1 tyrosine phosphorylation. Thus, these three kinase activities may be differentially coupled to the activation of the insulin receptor kinase activity via IRS‐1 and other possible cellular substrates. © 1995 Wiley‐Liss, Inc.