Document Detail


Multiple in vivo phosphorylated tyrosine phosphatase SHP-2 engages binding to Grb2 via tyrosine 584.
MedLine Citation:
PMID:  8959326     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SHP-2 (also named PTP1D, syp, or SH-PTP2) has been identified as a phosphotyrosine phosphatase comprising two src-homology-2 (SH2) domains. Upon growth factor stimulation, SHP-2 becomes tyrosine phosphorylated, thereby increasing its catalytic activity. Here, we identified SHP-2 to be phosphorylated on multiple tyrosine residues in response to different stimuli and unmasked the carboxyl-terminal tyrosine 584 as a major phosphorylation site in human cell lines. Tyrosine 584 shares, together with tyrosine 546, the consensus sequence pY-X-N-X, a characteristic of potential binding sites for the SH2 domain of growth factor receptor-bound protein 2 (Grb2). We show here that mutation of tyrosine 584, but not tyrosine 546, to phenylalanine totally abolished the binding of Grb2 to SHP-2. By using a systematic mutagenesis approach, phosphorylation of additional tyrosines in each of the SH2 domains of SHP-2 was detected after coexpression of epidermal growth factor receptor, but not after coexpression of platelet-derived growth factor receptor, whereas tyrosine 263 located in the interspace between SH2 and catalytic domain appears to be exclusively recognized by platelet-derived growth factor receptor. Immunoprecipitation of SHP-2 from a panel of mammary carcinoma cell lines copurifies several tyrosine phosphorylated proteins; the most prominent band has an apparent molecular weight of M(r) 115,000.
Authors:
W Vogel; A Ullrich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  7     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-03-07     Completed Date:  1997-03-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1589-97     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, Max-Planck-Institut für Blochemie, Martinsried, Germany. vogel@mshri.on.ca
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing*
Animals
Blotting, Western
Cell Line / chemistry,  enzymology
Electrophoresis, Gel, Two-Dimensional
GRB2 Adaptor Protein
Humans
Intracellular Signaling Peptides and Proteins
Kidney / cytology
Mutagenesis / physiology
Phosphorylation
Phosphotyrosine / metabolism
Protein Binding / physiology
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / chemistry,  genetics,  metabolism*
Proteins / metabolism*
Rabbits
Receptor, Epidermal Growth Factor / metabolism
SH2 Domain-Containing Protein Tyrosine Phosphatases
Serine / metabolism
Signal Transduction / physiology
Threonine / metabolism
Tyrosine / metabolism*
src Homology Domains / physiology
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/GRB2 Adaptor Protein; 0/GRB2 protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Proteins; 21820-51-9/Phosphotyrosine; 55520-40-6/Tyrosine; 56-45-1/Serine; 72-19-5/Threonine; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 3.1.3.48/PTPN11 protein, human; EC 3.1.3.48/PTPN6 protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 11; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 6; EC 3.1.3.48/Protein Tyrosine Phosphatases; EC 3.1.3.48/SH2 Domain-Containing Protein Tyrosine Phosphatases

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