Integrin αvβ3 mediates platelet-derived growth factor-BB-stimulated collagen gel contraction in cells expressing signaling deficient integrin α2β1

Gunilla Grundström, Deane F. Mosher, Takao Sakai, Kristofer Rubin

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The interplay between the collagen-binding integrin, α2β1, and platelet-derived growth factor (PDGF) receptors in the context of functional interactions with collagen was studied. We expressed either wild-type α2β1 (α2β1A) or α2β1 with a Y783/795F mutation in the cytoplasmic tail of the β1 subunit (α2β1Amut) in the β1-null fibroblastic cell line, GD25. GD25 cells lack endogenous expression of the α1 and α2 integrin subunits and do not adhere to collagen even after transfection with β1A. Cells expressing α2β1Amut contracted three-dimensional collagen lattices less efficiently than those expressing α2β1A. PDGF-BB significantly stimulated lattice contraction by GD25-α2β1Amut cells. Both cell types responded chemotactically to PDGF-BB. Focal adhesion kinase (FAK) and p130Cas were phosphorylated when GD25-α2β1A cells, but not GD25-α2β1Amut cells were seeded on collagen-coated dishes. Subsequent treatment with PDGF-BB further increased phosphorylation of FAK and p130Cas only in GD25-α2β1A cells. However, when cultured within collagen lattices, FAK and p130Cas phosphorylation were stimulated in both α2β1A- and α2β1Amut-expressing cells but further phosphorylation, in response to subsequent treatment with PDGF-BB, was seen only in GD25-α2β1A cells. We show that the stimulatory effects of PDGF-BB on collagen gel contraction and chemotaxis by GD25-α2β1Amut cells were mediated by the αvβ3 integrin. Phosphorylation of p130Cas, but not FAK, in GD25-α2β1Amut cells seeded in collagen lattices also depended on αvβ3. Our results show that PDGF-BB stimulation of fibroblast-collagen interactions is mediated by the αvβ3 integrin when β1 integrin function is impaired.

Original languageEnglish
Pages (from-to)463-473
Number of pages11
JournalExperimental Cell Research
Volume291
Issue number2
DOIs
Publication statusPublished - 01-12-2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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