P21-activated kinase 1: Convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human broblasts

Sangmyung Rhee, Frederick Grinnell

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Abstract

Fibroblast three-dimensional collagen matrix culture provides a tissue-like model that can be used to analyze cell form and function. The physiological agonists platelet-derived growth factor (PDGF) and lysophosphatidic acid (LPA) both stimulate human broblasts to contract oating collagen matrices. In this study, we show that the PDGF and LPA signaling pathways required for matrix contraction converge on p21-activated kinase 1 (PAK1) and its downstream effector cofilin1 and that contraction depends on cellular ruffling activity, rather than on the protrusion and retraction of cellular dendritic extensions. We also show that, depending on the agonist, different Rho effectors cooperate with PAK1 to regulate matrix contraction, Rho kinase in the case of PDGF and mDia1 in the case of LPA. These findings establish a unified framework for understanding the cell signaling pathways involved in fibroblast contraction of floating collagen matrices.

Original languageEnglish (US)
Pages (from-to)423-432
Number of pages10
JournalJournal of Cell Biology
Volume172
Issue number3
DOIs
StatePublished - Jan 30 2006

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ASJC Scopus subject areas

  • Cell Biology

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