The 60 kDa insulin receptor substrate functions like an IRS protein (pp60IRS3) in adipose cells.
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.
Smith-Hall
J
J
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Pons
S
S
Patti
M E
ME
Burks
D J
DJ
Yenush
L
L
Sun
X J
XJ
Kahn
C R
CR
White
M F
MF
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D007163:Immunosorbent Techniques; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008970:Molecular Weight; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D013737:Testis / Q000737:chemistry
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526296:Irs1 protein, rat; C526298:Irs2 protein, mouse; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011972:Receptor, Insulin