Restoration of β1A integrins is required for lysophosphatidic acid- induced migration of β1-null mouse fibroblastic cells

Takao Sakai, Olivier Peyruchaud, Reinhard Fässler, Deane F. Mosher

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50 Citations (Scopus)

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., Fassler, 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 expressed edg-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.

Original languageEnglish
Pages (from-to)19378-19382
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number31
DOIs
Publication statusPublished - 31-07-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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