Insulin stimulates the tyrosine dephosphorylation of pp125 focal adhesion kinase.
The phosphorylation state of pp125 focal adhesion kinase in response to insulin was examined in parental and transfected Rat-1 fibroblasts expressing both wild-type (HIRc cells) and mutant human insulin receptor cDNAs lacking the C-terminal twin tyrosine phosphorylation sites (YF2 cells) or a deletion mutant lacking the distal 43 amino acids of the beta-subunit (delta CT cells). In HIRc cells insulin stimulated the tyrosine dephosphorylation of pp125fak, whereas IGF-I did not. In contrast, the tyrosine phosphorylation state of pp125fak was unchanged in the parental Rat-1 fibroblasts and the YF2 or delta CT mutant cell lines in response to insulin. Analysis of the supernatants revealed that pp125fak was only one component of the major M(r), 120-130-kDa phosphotyrosine band seen in HIRc cells. We conclude that: 1) in contrast to other growth factors, insulin stimulates the dephosphorylation of pp125fak; 2) the presence of the insulin receptor C-terminal tyrosines 1328 and 1334 is required for the insulin-stimulated tyrosine dephosphorylation of pp125fak, suggesting a possible SH2 domain-dependent interaction; 3) insulin may modulate integrin-mediated signaling through pp125fak by altering the phosphorylation state of pp125fak.
Department of Medicine, University of California San Diego, La Jolla 92093-0673.
T S
TS
Pillay
T
T
Sasaoka
J M
JM
Olefsky
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007328:Insulin / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D007328:Insulin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat