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Molecular and Cellular Biology, March 2001, p. 1565-1572, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1565-1572.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Selective Expression of an Endogenous Inhibitor of FAK Regulates Proliferation and Migration of Vascular Smooth Muscle Cells

Joan M. Taylor,1 Christopher P. Mack,2 Kate Nolan,1 Christopher P. Regan,2 Gary K. Owens,2 and J. Thomas Parsons1,*

Departments of Microbiology1 and Molecular Physiology and Biological Physics,2 Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908

Received 18 October 2000/Returned for modification 22 November 2000/Accepted 7 December 2000

Extracellular matrix signaling via integrin receptors is important for smooth muscle cell (SMC) differentiation during vasculogenesis and for phenotypic modulation of SMCs during atherosclerosis. We previously reported that the noncatalytic carboxyl-terminal protein binding domain of focal adhesion kinase (FAK) is expressed as a separate protein termed FAK-related nonkinase (FRNK) and that ectopic expression of FRNK can attenuate FAK activity and integrin-dependent signaling (A. Richardson and J. T. Parsons, Nature 380:538-540, 1996). Herein we report that in contrast to FAK, which is expressed ubiquitously, FRNK is expressed selectively in SMCs, with particularly high levels observed in conduit blood vessels. FRNK expression was low during embryonic development, was significantly upregulated in the postnatal period, and returned to low but detectable levels in adult tissues. FRNK expression was also dramatically upregulated following balloon-induced carotid artery injury. In cultured rat aortic smooth muscle cells, overexpression of FRNK attenuated platelet-derived growth factor (PDGF)-BB-induced migration and also dramatically inhibited [3H]thymidine incorporation upon stimulation with PDGF-BB or 10% serum. These effects were concomitant with a reduction in SMC proliferation. Taken together, these data indicate that FRNK acts as an endogenous inhibitor of FAK signaling in SMCs. Furthermore, increased FRNK expression following vascular injury or during development may alter the SMC phenotype by negatively regulating proliferative and migratory signals.

* Corresponding author. Mailing address: Department of Microbiology, Box 441, Health Sciences Center, University of Virginia, Charlottesville, VA 22908. Phone: (804) 924-5395. Fax: (804) 982-1071. E-mail: jtp{at}virginia.edu.

Molecular and Cellular Biology, March 2001, p. 1565-1572, Vol. 21, No. 5
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.5.1565-1572.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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