Insulin receptor tyrosine kinase activity accounts for tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), but the serine kinase(s) responsible for serine phosphorylation of IRS-1 is(are) unknown. In vitro kinase assays performed on PI3-kinase and IRS-1 immunoprecipitates demonstrated insulin-dependent serine phosphorylation of IRS-1. IRS-1 was associated with both insulin-dependent and independent serine kinases. Only the insulin-dependent serine kinase preferred Mn2+ over Mg2+ and was recovered from cell lysates containing dithiothreitol. In complexes of tyrosine phosphorylated recombinant IRS-1 and PI3-kinase, phosphorylation of IRS-1 was associated with decreased phosphorylation of the p85 subunit of PIS-kinase. These results are consistent with PI3-kinase being responsible for insulin-dependent serine phosphorylation of IRS-1 and suggest that this phosphorylation reaction may affect functions of both IRS-1 and the PI3-kinase.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jan 5 1995|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology