Restoration of β1A Integrins is Required for Lysophosphatidic Acid-induced Migration of β1-null Mouse Fibroblastic Cells*
- From the ‡Departments of Medicine and Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin 53706 and the §Department of Experimental Pathology, Lund University, 221 85 Lund, Sweden
Abstract
Cells lacking the β1 integrin subunit or expressing β1A 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 β1A integrins on lysophosphatidic acid (LPA)-induced migration of fibroblastic cells derived from β1-null mouse embryonic stem cells. These cells expressededg-2, a G-protein-linked receptor for LPA, as well as the related edg-1 receptor. Cells expressing wild type β1A demonstrated enhanced cell migration across filters coated with gelatin or adhesive proteins in response to LPA, whereas β1-deficient cells lacked LPA-induced cell migratory ability. Checkerboard analyses indicated that LPA causes both chemotaxis and chemokinesis of β1-replete cells. Cells expressing β1A 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 β1A integrin is required for cell migration induced by LPA and that the cytoplasmic domain of ligated β1A interacts with pathways that are common to both receptor tyrosine kinase and G-protein-linked receptor signaling.
Footnotes
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↵* This work was supported by National Institutes of Health Grants HL21644 and HL54462, fellowship funds from the Cell Science Research Foundation and Marion Merrill Dow (to T. S.), a postdoctoral grant from Sanofi Association for Thrombosis Research (to O. P.), and a grant from the Swedish National Research Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed: Depts. of Medicine and Biomolecular Chemistry, University of Wisconsin-Madison, 4285B, Medical Science Center, 1300 University Ave., Madison, WI 53706. Tel.: 608-262-1576; Fax: 608-263-4969; E-mail:dfmosher{at}facstaff.wisc.edu.
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↵1 The abbreviations used are: LPA, lysophosphatidic acid; edg, endothelial differentiation gene; EGF, epidermal growth factor; PDGF, platelet-derived growth factor; vzg-1, ventricular zone gene-1; BSA, bovine serum albumin; RT-PCR, reverse transcription-polymerase chain reaction.
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↵2 O. Peyruchaud and D. F. Mosher, submitted for publication.
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↵3 T. Panetti, O. Peyruchaud, and D. F. Mosher, manuscript in preparation.
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↵4 m. K. Magnusson and D. F. Mosher, submitted for publication.
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- Received April 30, 1998.
- Revision received June 9, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
