Decreased PDGF receptor kinase activity in fibroblasts contracting stressed collagen matrices

Ying Chun Lin, Chin Han Ho, Frederick Grinnell

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Fibroblasts cultured in mechanically stressed collagen matrices proliferate, whereas cells in floating collagen matrices become quiescent. Previous research indicated that one factor contributing to cell quiescence in floating matrices was reduced receptor autophosphorylation in response to PDGF stimulation (i.e., PDGF receptor desensitization). To learn more about the mechanism of PDGF receptor desensitization, we analyzed changes in PDGF receptor autophosphorylation and receptor kinase activity after stressed collagen matrices were switched to floating conditions, which results in rapid cell contraction and dissipation of mechanical stress. PDGF receptor desensitization occurred during contraction stimulated by serum but not in the absence of serum, and desensitization was prevented by inhibitors of contraction but not by inhibitors of the contraction-activated cyclic AMP signaling pathway. Receptor desensitization resulted from decreased receptor kinase activity rather than from elevated protein tyrosine phosphatase activity, and only receptors unoccupied at the time of contraction were affected. After contraction, radiolabeled PDGF binding to the cells was decreased, which suggested that receptor desensitization resulted from a contraction-dependent change in receptor availability or affinity.

Original languageEnglish (US)
Pages (from-to)377-387
Number of pages11
JournalExperimental Cell Research
Volume240
Issue number2
DOIs
StatePublished - May 1 1998

ASJC Scopus subject areas

  • Cell Biology

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