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Titolo:
Distinct functions of the two protein tyrosine phosphatase domains of LAR (leukocyte common antigen-related) on tyrosine dephosphorylation of insulinreceptor
Autore:
Tsujikawa, K; Kawakami, N; Uchino, Y; Ichijo, T; Furukawa, T; Saito, H; Yamamoto, H;
Indirizzi:
Osaka Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Suita, Osaka 5650871, Japan Osaka Univ Suita Osaka Japan 5650871 Immunol, Suita, Osaka 5650871, Japan Kagoshima Univ, Fac Med, Inst Canc Res, Dept Canc Chemotherapy, Kagoshima 8908520, Japan Kagoshima Univ Kagoshima Japan 8908520 therapy, Kagoshima 8908520, Japan Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA HarvardUniv Boston MA USA 02115 a Farber Canc Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 em & Mol Pharmacol, Boston, MA 02115 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 2, volume: 15, anno: 2001,
pagine: 271 - 280
SICI:
0888-8809(200102)15:2<271:DFOTTP>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
SIGNAL-TRANSDUCTION; HOMOPHILIC BINDING; CRYSTAL-STRUCTURE; IN-VIVO; LIGAND; ALPHA; BETA; EXPRESSION; KINASE; MU;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Tsujikawa, K Osaka Univ, Grad Sch Pharmaceut Sci, Dept Immunol, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan Osaka Univ 1-6 Yamadaoka Suita Osaka Japan5650871 871, Japan
Citazione:
K. Tsujikawa et al., "Distinct functions of the two protein tyrosine phosphatase domains of LAR (leukocyte common antigen-related) on tyrosine dephosphorylation of insulinreceptor", MOL ENDOCR, 15(2), 2001, pp. 271-280

Abstract

Most receptor-like, transmembrane protein tyrosine phosphatases (PTPases),such as CD45 and the leukocyte common antigen-related (LAR) molecule, havetwo tandemly repeated PTPase domains in the cytoplasmic segment. The role of each PTPase domain in mediating PTPase activity remains unclear; however, it has been proposed that PTPase activity is associated with only the first of the two domains, PTPase domain 1, and the membrane-distal PTPase domain 2, which has no catalytic activity, would regulate substrate specificity. In this paper, we examine the function of each PTPase domain of LAR in vivo using a potential physiological substrate, namely insulin receptor, and LAR mutant proteins in which the conserved cysteine residue was changed to a serine residue in the active site of either or both PTPase domains. LAR associated with and preferentially dephosphorylated the insulin receptor that was tyrosine phosphorylated by insulin stimulation. Its association was mediated by PTPase domain 2, because the mutation of Cys-1813 to Ser in domain 2 resulted in weakening of the association. The Cys-1522 to Ser mutant protein, which is defective in the LAR PTPase domain 1 catalytic site, was tightly associated with tyrosine-phosphorylated insulin receptor, but failedto dephosphorylate it, indicating that LAR PTPase domain 1 is critical fordephosphorylation of tyrosine-phosphorylated insulin receptor. This hypothesis was further confirmed by using LAR mutants in which either PTPase domain 1 or domain 2 was deleted. Moreover, the association of the extracellular domains of both LAR and insulin receptor was supported by using the LAR mutant protein without the two PTPase domains. LAR was phosphorylated by insulin receptor tyrosine kinase and autodephosphorylated by the catalytic activity of the PTPase domain 1. These results indicate that each domain of LAR plays distinct functional roles through phosphorylation and dephosphorylation in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 13:22:52