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Published 30 January 2006. doi:10.1083/jcb.200505175
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 3, 423-432
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Article

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

Sangmyung Rhee and Frederick Grinnell

Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX 75390

Correspondence to Frederick Grinnell: frederick.grinnell{at}utsouthwestern.edu

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 fibroblasts to contract floating 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.

Abbreviations used in this paper: 2D, two-dimensional; 3D, three-dimensional; ADF, actin-depolymerizing factor; LPA, lysophosphatidic acid; PAK1, p21-activated kinase; PI3, phosphoinositide 3; SH3, Src homology domain; siRNA, small interfering RNA.


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