The 60 kDa insulin receptor substrate functions like an IRS protein (pp60IRS3) in adipose cells

Biochemistry. 1997 Jul 8;36(27):8304-10. doi: 10.1021/bi9630974.

Abstract

The 60 kDa insulin receptor substrate in rat adipocytes that binds to the PI-3 kinase displays several functional characteristics in common with the IRS proteins; so we propose the name pp60(IRS3) to distinguish it from other tyrosine phosphorylated proteins of similar size. During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-1 or IRS-2. In mice lacking IRS-1, p85 associated more strongly with pp60(IRS3) than with IRS-2, suggesting that pp60(IRS3) provides an alternate pathway in these cells. Synthetic peptides containing two phosphorylated YMPM motifs displace pp60(IRS3) and IRS-1 from alphap85 immune complexes, suggesting that pp60(IRS3), like IRS-1, engages both SH2 domains in p85. Moreover, pp60(IRS3) binds to immobilized peptides containing a phosphorylated NPXY motif, suggesting that it contains a PTB domain with similar specificity to that in IRS-1. The cloning of pp60(IRS3) will reveal a new member of the IRS protein family which mediates insulin receptor signals in a narrow range of tissues.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Immunosorbent Techniques
  • Insulin / pharmacology
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Molecular Weight
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Phosphotyrosine / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Insulin / metabolism*
  • Testis / chemistry

Substances

  • Insulin
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Irs1 protein, mouse
  • Irs1 protein, rat
  • Irs2 protein, mouse
  • Irs2 protein, rat
  • Phosphoproteins
  • Phosphotyrosine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Receptor, Insulin