The p21 (Cdc42/Rac) activated kinase Pak1 regulates cell morphology and polarity in most, if not all, eukaryotic cells. We and others have established that Pak's effects on these parameters are mediated by changes in the organization of cortical actin. Because cell motility requires polarized rearrangements of the actin/myosin cytoskeleton, we examined the role of Pak1 in regulating cell movement. We established clonal tetracycline-regulated NIH-3T3 cell lines that inducibly express either wild-type Pak1, a kinase-dead, or constitutively-active forms of this enzyme, and examined the morphology, F-actin organization, and motility of these cells. Expression of any of these forms of Pak1 induced dramatic changes in actin organization which were not inhibited by coexpression of a dominant-negative form of Rac1. Cells inducibly expressing wild-type or constitutively-active Pak1 had large, polarized lamellipodia at the leading edge, were more motile than their normal counterparts when plated on a fibronectin-coated surface, and displayed enhanced directional movement in response to an immobilized collagen gradient. In contrast, cells expressing a kinase-dead form of Pak1 projected multiple lamellipodia emerging from different parts of the cell simultaneously. These cells, though highly motile, displayed reduced persistence of movement when plated on a fibronectin-coated surface and had defects in directed motility toward immobilized collagen. Expression of constitutively activated Pak1 was accompanied by increased myosin light chain (MLC) phosphorylation, whereas expression of kinase-dead Pak1 had no effect on MLC. These results suggest that Pak1 affects the phosphorylation state of MLC, thus linking this kinase to a molecule that directly affects cell movement.
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17 May 1999
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May 17 1999
p21-Activated Kinase 1 (Pak1) Regulates Cell Motility in Mammalian Fibroblasts
Mary Ann Sells,
Mary Ann Sells
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
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Jonathan T. Boyd,
Jonathan T. Boyd
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
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Jonathan Chernoff
Jonathan Chernoff
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
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Mary Ann Sells
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
Jonathan T. Boyd
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
Jonathan Chernoff
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
Address correspondence to Mary Ann Sells, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111. Tel.: (215)728-2485. Fax: (215)728-3616. E-mail: [email protected]
Received:
February 17 1999
Revision Received:
March 19 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1999
J Cell Biol (1999) 145 (4): 837–849.
Article history
Received:
February 17 1999
Revision Received:
March 19 1999
Citation
Mary Ann Sells, Jonathan T. Boyd, Jonathan Chernoff; p21-Activated Kinase 1 (Pak1) Regulates Cell Motility in Mammalian Fibroblasts . J Cell Biol 17 May 1999; 145 (4): 837–849. doi: https://doi.org/10.1083/jcb.145.4.837
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