Document Detail

Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility.
MedLine Citation:
PMID:  10082579     Owner:  NLM     Status:  MEDLINE    
The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins. On the other hand, IGF-I promotes the association of insulin receptor substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected cells. This impairment of cell migration is recovered by reintroduction of a catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity participates in the integrin deactivation process. Although SHP-2 regulates mitogen-activated protein kinase activity, the mitogen-activated protein kinase kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The role of SHP-2 as a general regulator of cell chemotaxis induced by other chemotactic agents and integrins is discussed.
S Mañes; E Mira; C Gómez-Mouton; Z J Zhao; R A Lacalle; C Martínez-A
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  19     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-04-20     Completed Date:  1999-04-20     Revised Date:  2013-04-17    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3125-35     Citation Subset:  IM    
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain.
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MeSH Terms
Cell Adhesion / physiology
Cell Adhesion Molecules / metabolism*
Cell Movement / physiology*
Chemokine CCL5 / pharmacology
Chemotactic Factors / metabolism
Chemotaxis / physiology
Cytoskeletal Proteins / metabolism
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Insulin Receptor Substrate Proteins
Insulin-Like Growth Factor I / pharmacology*
Integrins / metabolism
Intracellular Signaling Peptides and Proteins
Models, Biological
Neoplasm Invasiveness
Phosphoproteins / metabolism
Protein Binding
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / genetics,  metabolism*
Protein-Tyrosine Kinases / metabolism*
Receptor Cross-Talk / physiology*
Receptor, IGF Type 1 / metabolism
Signal Transduction
Tumor Cells, Cultured
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Chemokine CCL5; 0/Chemotactic Factors; 0/Cytoskeletal Proteins; 0/IRS1 protein, human; 0/Insulin Receptor Substrate Proteins; 0/Integrins; 0/Intracellular Signaling Peptides and Proteins; 0/PXN protein, human; 0/Paxillin; 0/Phosphoproteins; 67763-96-6/Insulin-Like Growth Factor I; EC Kinases; EC, IGF Type 1; EC Adhesion Kinase 1; EC Adhesion Protein-Tyrosine Kinases; EC protein, human; EC protein, human; EC protein, human; EC Tyrosine Phosphatase, Non-Receptor Type 1; EC Tyrosine Phosphatase, Non-Receptor Type 11; EC Tyrosine Phosphatase, Non-Receptor Type 6; EC Tyrosine Phosphatases

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