| 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 |
Related Documents
:
|
21878656 - Antitumoral effects of calcitriol in basal cell carcinomas involve inhibition of hedgeh... 22193776 - Xenopus paraxial protocadherin inhibits wnt/β-catenin signalling via casein kinase 2β. 12746446 - Glucose stimulates the tyrosine phosphorylation of crk-associated substrate in pancreat... 8452536 - Activation of human platelets by peroxovanadate is associated with tyrosine phosphoryla... 10617676 - Involvement of protein kinase c-gamma in il-1beta-induced cyclooxygenase-2 expression i... 16360946 - Insect freeze tolerance: roles of protein phosphatases and protein kinase a. |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Insulin promotion of colon tumors in rats.
Next Document: Cell cycle-independent regulation of p21Waf1/Cip1 and retinoblastoma protein during okadaic acid-ind...