Restoration of beta1A integrins is required for lysophosphatidic acid-induced migration of beta1-null mouse fibroblastic cells.
Cells lacking the beta1 integrin subunit or expressing beta1A with certain cytoplasmic mutations have poor directed cell migration to platelet-derived growth factor or epidermal growth factor, ligands of receptor tyrosine kinases (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538). We investigated the effect of expression of beta1A integrins on lysophosphatidic acid (LPA)-induced migration of fibroblastic cells derived from beta1-null mouse embryonic stem cells. These cells expressed edg-2, a G-protein-linked receptor for LPA, as well as the related edg-1 receptor. Cells expressing wild type beta1A demonstrated enhanced cell migration across filters coated with gelatin or adhesive proteins in response to LPA, whereas beta1-deficient cells lacked LPA-induced cell migratory ability. Checkerboard analyses indicated that LPA causes both chemotaxis and chemokinesis of beta1-replete cells. Cells expressing beta1A with mutations of prolines or tyrosines in conserved cytoplasmic NPXY motifs, threonine in the inter-motif sequence, or a critical aspartic acid in the extracellular domain had low migratory responses to LPA. These findings indicate that active beta1A integrin is required for cell migration induced by LPA and that the cytoplasmic domain of ligated beta1A interacts with pathways that are common to both receptor tyrosine kinase and G-protein-linked receptor signaling.
Departments of Medicine and Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
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T
Sakai
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Peyruchaud
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R
Fässler
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DF
Mosher
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D019012:Integrin beta1 / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D019096:Vitronectin / Q000378:metabolism
D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D019096:Vitronectin; D004815:Epidermal Growth Factor; D005780:Gelatin; D020794:Receptor Protein-Tyrosine Kinases