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

The interplay between the collagen-binding integrin, 21, and platelet-derived growth factor (PDGF) receptors in the context of functional interactions with collagen was studied. We expressed either wild-type 2 1( 21A) or 21 with a Y783/795F mutation in the cytoplasmic tail of the 1 subunit (21Amut) in the 1-null fibroblastic cell line, GD25. GD25 cells lack endogenous expression of the 1 and 2 integrin subunits and do not adhere to collagen even after transfection with 1A. Cells expressing 21Amut contracted three-dimensional collagen lattices less efficiently than those expressing 21A. PDGF-BB significantly stimulated lattice contraction by GD25-21Amut cells. Both cell types responded chemotactically to PDGF-BB. Focal adhesion kinase (FAK) and p130 Cas were phosphorylated when GD25-21A cells, but not GD25-21Amut cells were seeded on collagen-coated dishes. Subsequent treatment with PDGF-BB further increased phosphorylation of FAK and p130 Cas only in GD25-21A cells. However, when cultured within collagen lattices, FAK and p130 Cas phosphorylation were stimulated in both 21A- and 21Amut-expressing cells but further phosphorylation, in response to subsequent treatment with PDGF-BB, was seen only in GD25-21A cells. We show that the stimulatory effects of PDGF-BB on collagen gel contraction and chemotaxis by GD25-21Amut cells were mediated by the v3 integrin. Phosphorylation of p130 Cas , but not FAK, in GD25-21Amut cells seeded in collagen lattices also depended on v3. Our results show that PDGF-BB stimulation of fibroblast‐ collagen interactions is mediated by thev3 integrin when 1 integrin function is impaired.