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Molecular and Cellular Biology, April 2000, p. 2619-2627, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

p21-Activated Kinase 1 Plays a Critical Role in Cellular Activation by Nef

Oliver T. Fackler,1 Xiaobin Lu,2 Jeffrey A. Frost,3 Matthias Geyer,1 Bing Jiang,1 Wen Luo,1 Arie Abo,2 Arthur S. Alberts,4 and B. Matija Peterlin1,*

Howard Hughes Medical Institute, Departments of Medicine, Microbiology, and Immunology,1 and Cancer Research Institute,4 University of California at San Francisco, San Francisco, California 94143-0703; Onyx Pharmaceuticals, Richmond, California 948062; and University of Texas Southwestern Medical Center, Dallas, Texas 75235-90413

Received 2 September 1999/Returned for modification 27 October 1999/Accepted 14 January 2000

The activation of Nef-associated kinase (NAK) by Nef from human and simian immunodeficiency viruses is critical for efficient viral replication and pathogenesis. This induction occurs via the guanine nucleotide exchange factor Vav and the small GTPases Rac1 and Cdc42. In this study, we identified NAK as p21-activated kinase 1 (PAK1). PAK1 bound to Nef in vitro and in vivo. Moreover, the induction of cytoskeletal rearrangements such as the formation of trichopodia, the activation of Jun N-terminal kinase, and the increase of viral production were blocked by an inhibitory peptide that targets the kinase activity of PAK1 (PAK1 83-149). These results identify NAK as PAK1 and emphasize the central role its kinase activity plays in cytoskeletal rearrangements and cellular signaling by Nef.

* Corresponding author. Mailing address: UCSF Box 0703, 3rd and Parnassus Ave., San Francisco, CA 94143-0703. Phone: (415) 502-1902. Fax: (415) 502-1901. E-mail: matija{at}itsa.ucsf.edu.

Molecular and Cellular Biology, April 2000, p. 2619-2627, Vol. 20, No. 7
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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