Src homology 2 domains of protein tyrosine phosphatase are associated in vitro with both the insulin receptor and insulin receptor substrate-1 via different phosphotyrosine motifs.
To clarify the role of protein tyrosine phosphatase containing Src homology 2 (SH2) regions on insulin signaling, we investigated the interactions among the insulin receptor, a pair of SH2 domains of SH-PTP2 coupled to glutathione-S-transferase (GST) and insulin receptor substrate-1 (IRS-1)-GST fusion protein (amino-portion, IRS-IN; carboxyl portion, IRS-1C). GST-SH2 protein of SH-PTP2 bound to the wild type insulin receptor, but not to that with a carboxyl-terminal mutation (Y/F2). Furthermore, even though Y/F2 receptors were used, the SH2 protein was also co-immunoprecipitated with IRS-IC, but not with IRS-IN. These results indicate that SH2 domains of SH-PTP2 can directly associate with the Y1322TXM motif on the carboxyl terminus of insulin receptors and also may bind to the carboxyl portion of IRS-1, possibly via the Y1172IDL motif in vitro.
Ugi
S
S
Third Department of Medicine, Shiga University of Medical Science, Japan.
Maegawa
H
H
Olefsky
J M
JM
Shigeta
Y
Y
Kashiwagi
A
A
D001665:Binding Sites; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000737:chemistry; D055504:Insulin Receptor Substrate Proteins; D015688:Oncogene Protein pp60(v-src) / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D005982:Glutathione Transferase; D011972:Receptor, Insulin; D015688:Oncogene Protein pp60(v-src); D017027:Protein Tyrosine Phosphatases