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.
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30 January 2006
Article|
January 30 2006
P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts
Sangmyung Rhee,
Sangmyung Rhee
Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX 75390
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Frederick Grinnell
Frederick Grinnell
Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX 75390
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Sangmyung Rhee
Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX 75390
Frederick Grinnell
Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX 75390
Correspondence to Frederick Grinnell: [email protected]
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.
Received:
May 31 2005
Accepted:
December 28 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 172 (3): 423–432.
Article history
Received:
May 31 2005
Accepted:
December 28 2005
Citation
Sangmyung Rhee, Frederick Grinnell; P21-activated kinase 1: convergence point in PDGF- and LPA-stimulated collagen matrix contraction by human fibroblasts . J Cell Biol 30 January 2006; 172 (3): 423–432. doi: https://doi.org/10.1083/jcb.200505175
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