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J Biol Chem, Vol. 273, Issue 31, 19378-19382, July 31, 1998
From the Cells lacking the
Restoration of
1A Integrins is Required for
Lysophosphatidic Acid-induced Migration of
1-null
Mouse Fibroblastic Cells
,
,
Departments of Medicine and Biomolecular
Chemistry, University of Wisconsin, Madison, Wisconsin 53706 and
the § Department of Experimental Pathology, Lund University,
221 85 Lund, Sweden
1 integrin
subunit or expressing
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
1A integrins on lysophosphatidic acid (LPA)-induced migration of fibroblastic cells derived from
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
1A demonstrated enhanced cell migration across filters
coated with gelatin or adhesive proteins in response to LPA, whereas
1-deficient cells lacked LPA-induced cell migratory
ability. Checkerboard analyses indicated that LPA causes both
chemotaxis and chemokinesis of
1-replete cells. Cells
expressing
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
1A integrin is required for cell migration
induced by LPA and that the cytoplasmic domain of ligated
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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