PMID: 11342028May 9, 2001Paper

A model of activation of the protein tyrosine phosphatase SHP-2 by the human leptin receptor

Biochimica Et Biophysica Acta
A LöthgrenS R James

Abstract

Signalling through the leptin receptor has been shown to activate the SH2 domain-containing tyrosine phosphatase SHP-2 through tyrosine phosphorylation. The human leptin receptor contains five tyrosine residues in the cytoplasmic domain that may become phosphorylated. We show here using BIAcore studies, wherein binding of peptides to SHP-2 was detected, that peptides corresponding to sequences containing phosphotyrosines 974 and 986 (LR974P and LR986P, respectively) from the leptin receptor cytoplasmic domain were the only two peptides that bound to the enzyme. Binding of LR974P to SHP-2 was inhibited in a dose-dependent fashion by orthovanadate, whereas binding of LY986P was not, indicating that the enzyme binds to these peptides through different sites. Only the leptin receptor-derived peptide corresponding to tyrosine 974 was dephosphorylated by recombinant purified SHP-2. Time courses of the reaction were complex, and fitted a two exponent rate equation. Preincubation of SHP-2 with LR986P markedly activated the enzyme at early time points and time courses of the activated enzyme fitted a single exponential first order rate equation. We propose that LR974P binds to the active site of SHP-2, whereas LR986P may bind to the N- ...Continue Reading

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Citations

Mar 12, 2013·Endocrine Reviews·Hyun-Seuk MoonChristos S Mantzoros
Apr 10, 2003·Biochemical and Biophysical Research Communications·Itamar GorenStefan Frank
Dec 26, 2002·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Jan 30, 2004·The Journal of Pharmacology and Experimental Therapeutics·Charlotta LiljebrisStephen R James
May 22, 2002·Cellular Signalling·Gary Sweeney

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