Document Detail


Synergism among lysophosphatidic acid, beta1A integrins, and epidermal growth factor or platelet-derived growth factor in mediation of cell migration.
MedLine Citation:
PMID:  10336439     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GD25 cells lacking the beta1 integrin subunit or expressing beta1A with certain cytoplasmic mutations have poor directed cell migration to platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), ligands of receptor tyrosine kinases, or to lysophosphatidic acid (LPA), a ligand of G-protein-coupled receptors (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538 and Sakai, T., Peyruchaud, O., Fässler, R., and Mosher, D. F. (1998) J. Biol. Chem. 273, 19378-19382). We demonstrate here that LPA synergizes with signals induced by beta1A integrins and ligated EGF or PDGF receptors to modulate migration. When LPA was mixed with EGF or PDGF, migration was greater than with EGF or PDGF alone. The enhancement was greater for beta1A-expressing cells than for beta1-null cells. Cells expressing beta1A with mutations of prolines or tyrosines in conserved cytoplasmic NPXY motifs had blunted migratory responses to mixtures of LPA and EGF or PDGF. The major effects on beta1A-expressing cells of LPA when combined with EGF or PDGF were to sensitize cells so that maximal responses were obtained with >10-fold lower concentrations of growth factor and increase the chemokinetic component of migration. Sensitization by LPA was lost when cells were preincubated with pertussis toxin or C3 exotransferase. There was no evidence for transactivation or sensitization of receptors for EGF or PDGF by LPA. EGF or PDGF and LPA caused activation of mitogen-activated protein kinase by pertussis toxin-insensitive and -sensitive pathways respectively, but activation was not additive. These findings indicate that signaling pathways initiated by the cytoplasmic domains of ligated beta1A integrins and tyrosine kinase receptors interact with signaling pathways initiated by LPA to facilitate directed cell migration.
Authors:
T Sakai; J M de la Pena; D F Mosher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  274     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-06-29     Completed Date:  1999-06-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  15480-6     Citation Subset:  IM    
Affiliation:
Departments of Medicine and Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
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MeSH Terms
Descriptor/Qualifier:
ADP Ribose Transferases / pharmacology
Animals
Antigens, CD29 / pharmacology*
Botulinum Toxins*
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Cell Line
Cell Movement / drug effects*
Drug Synergism
Enzyme Activation / drug effects
Epidermal Growth Factor / pharmacology*
Fibronectins / metabolism
Gelatin / metabolism
Lysophospholipids / pharmacology*
Mice
Mutation
Pertussis Toxin
Phosphotyrosine / analysis
Platelet-Derived Growth Factor / pharmacology*
Receptor, Epidermal Growth Factor / metabolism
Receptors, Platelet-Derived Growth Factor / metabolism
Signal Transduction / drug effects
Virulence Factors, Bordetella / pharmacology
Vitronectin / metabolism
Grant Support
ID/Acronym/Agency:
HL21644/HL/NHLBI NIH HHS; HL56396/HL/NHLBI NIH HHS; T32 GM07215/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD29; 0/Botulinum Toxins; 0/Fibronectins; 0/Lysophospholipids; 0/Platelet-Derived Growth Factor; 0/Virulence Factors, Bordetella; 0/Vitronectin; 21820-51-9/Phosphotyrosine; 62229-50-9/Epidermal Growth Factor; 9000-70-8/Gelatin; EC 2.4.2.-/ADP Ribose Transferases; EC 2.4.2.-/exoenzyme C3, Clostridium botulinum; EC 2.4.2.31/Pertussis Toxin; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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