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J Biol Chem, Vol. 273, Issue 31, 19378-19382, July 31, 1998

Restoration of beta 1A Integrins is Required for Lysophosphatidic Acid-induced Migration of beta 1-null Mouse Fibroblastic Cells

Takao SakaiDagger , Olivier PeyruchaudDagger , Reinhard Fässler§, and Deane F. MosherDagger

From the Dagger  Departments of Medicine and Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706 and the § Department of Experimental Pathology, Lund University, 221 85 Lund, Sweden

Cells lacking the beta 1 integrin subunit or expressing beta 1A 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 beta 1A integrins on lysophosphatidic acid (LPA)-induced migration of fibroblastic cells derived from beta 1-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 beta 1A demonstrated enhanced cell migration across filters coated with gelatin or adhesive proteins in response to LPA, whereas beta 1-deficient cells lacked LPA-induced cell migratory ability. Checkerboard analyses indicated that LPA causes both chemotaxis and chemokinesis of beta 1-replete cells. Cells expressing beta 1A 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 beta 1A integrin is required for cell migration induced by LPA and that the cytoplasmic domain of ligated beta 1A interacts with pathways that are common to both receptor tyrosine kinase and G-protein-linked receptor signaling.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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