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

FEBS Letters

Maegawa, Hiroshi¹  Olefsky, Jerrold M.²  Shigeta, Yukio¹  Ugi, Satoshi¹  Kashiwagi, Atsunori¹ 

[1] Third Department of Medicine, Shiga University of Medical Science, Ohtsu, Shiga 520-21, Japan;Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA

关键词: Insulin receptor;    Protein tyrosine phosphatase;    Insulin receptor substrate-1;    Src homology 2;    Phosphotyrosine motif;    SH2;    Src homology 2;    1RS-1;    insulin receptor substrate-1;    IRS-1N;    amino-portion of IRS-1 (amino acids 434-764);    IRS-1C;    carboxyl-portion of IRS-1 (amino acids 1132-1235);    GST;    glutathione-5-transferase;    Y/F2;    a mutant receptor in which both carboxyl-terminal tyrosine residues (1316 and 1322) are replaced by phenylalanine;    PTK;    protein tyrosine kinase;    PTPase;    protein tyrosine phosphatase;    PtdIns 3'-kinase;    phosphatidylinositol 3−kinase;    WGA;    wheat germ agglutinin;    HIRc cells;    Rat 1 fibroblasts expressed with human insulin receptors;    α IR;    anti-insulin receptor antiserum;    α GST;    anti-GST antiserum;    PCR;    polymerase chain reaction;    PDGF;    platelet-derived growth factor;   

DOI  :  10.1016/0014-5793(94)80141-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 proteins (amino-portion, IRS-1N; 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-1C, but not with IRS-1N. 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 V¹¹⁷²IDL motif in vitro.

【 授权许可】

Unknown