SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates.
To investigate the role of Janus kinase family (JAK1 and JAK2) in insulin signaling, we assessed their insulin-induced associations with other molecules in the cells overexpressing insulin receptors (HIRc and CHO-IR). After insulin stimulation, pp185 proteins (insulin receptor substrate, IRS) were co-immunoprecipitated with both kinases by alpha JAK1 and alpha JAK2 antibodies. However, JAK2 constitutively associated with pp95 protein (IR beta). Moreover, JAK2 also constitutively bound to a protein tyrosine phosphatase containing Src 2 regions (SHPTP2), but JAK1 did not. In HIRc cells expressing PTPase-negative mutant SHPTP2, no association of JAK2 with either pp185 or pp95 was detected. Thus, SHPTP2 might serve as an adapter protein linking between JAK2 and IRS. These results suggest that JAK1 and JAK2 behave differently and they may constitute a new regulatory component in insulin signaling.
Third Department of Medicine, Shiga University of Medical Science, Japan.
H
H
Maegawa
A
A
Kashiwagi
T
T
Fujita
S
S
Ugi
M
M
Hasegawa
T
T
Obata
Y
Y
Nishio
H
H
Kojima
H
H
Hidaka
R
R
Kikkawa
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; C507906:Jak1 protein, rat; C507927:Jak2 protein, rat; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat