This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cotteret, S.
Right arrow Articles by Chernoff, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cotteret, S.
Right arrow Articles by Chernoff, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2003, p. 5526-5539, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5526-5539.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

p21-Activated Kinase 5 (Pak5) Localizes to Mitochondria and Inhibits Apoptosis by Phosphorylating BAD

Sophie Cotteret, Zahara M. Jaffer, Alexander Beeser, and Jonathan Chernoff*

Fox Chase Cancer Center, Philadelphia, Pennsylvania

Received 6 December 2002/ Returned for modification 27 January 2003/ Accepted 15 May 2003

Pak5 is the most recently identified and least understood member of the p21-activated kinase (Pak) family. This kinase is known to promote neurite outgrowth in vitro, but its localization, substrates, and effects on cell survival have not been reported. We show here that Pak5 has unique properties that distinguish it from all other members of the Pak family. First, Pak5, unlike Pak1, cannot complement an STE20 mutation in Saccharomyces cerevisiae. Second, Pak5 binds to the GTPases Cdc42 and Rac, but these GTPases do not regulate Pak5 kinase activity, which is constitutive and stronger than any other Pak. Third, Pak5 prevents apoptosis induced by camptothecin and C2-ceramide by phosphorylating BAD on Ser-112 in a protein kinase A-independent manner and prevents the localization of BAD to mitochondria, thereby inhibiting the apoptotic cascade that leads to apoptosis. Finally, we show that Pak5 itself is constitutively localized to mitochondria, and that this localization is independent of kinase activity or Cdc42 binding. These features make Pak5 unique among the Pak family and suggest that it plays an important role in apoptosis through BAD phosphorylation.

* Corresponding author. Mailing address: Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, PA 19111. Phone: (215) 728-5319. Fax: (215) 728-3616. E-mail: J_Chernoff{at}fccc.edu.

Molecular and Cellular Biology, August 2003, p. 5526-5539, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5526-5539.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Luo, S., Rubinsztein, D. C. (2009). Huntingtin promotes cell survival by preventing Pak2 cleavage. J. Cell Sci. 122: 875-885 [Abstract] [Full Text]  
  • Chan, P. M., Lim, L., Manser, E. (2008). PAK Is Regulated by PI3K, PIX, CDC42, and PP2C{alpha} and Mediates Focal Adhesion Turnover in the Hyperosmotic Stress-induced p38 Pathway. J. Biol. Chem. 283: 24949-24961 [Abstract] [Full Text]  
  • Luo, S., Mizuta, H., Rubinsztein, D. C. (2008). p21-activated kinase 1 promotes soluble mutant huntingtin self-interaction and enhances toxicity. Hum Mol Genet 17: 895-905 [Abstract] [Full Text]  
  • Rider, L., Shatrova, A., Feener, E. P., Webb, L., Diakonova, M. (2007). JAK2 Tyrosine Kinase Phosphorylates PAK1 and Regulates PAK1 Activity and Functions. J. Biol. Chem. 282: 30985-30996 [Abstract] [Full Text]  
  • Friedland, J. C., Lakins, J. N., Kazanietz, M. G., Chernoff, J., Boettiger, D., Weaver, V. M. (2007). {alpha}6beta4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-{kappa}B-dependent resistance to apoptosis in 3D mammary acini. J. Cell Sci. 120: 3700-3712 [Abstract] [Full Text]  
  • Saveanu, C., Rousselle, J.-C., Lenormand, P., Namane, A., Jacquier, A., Fromont-Racine, M. (2007). The p21-Activated Protein Kinase Inhibitor Skb15 and Its Budding Yeast Homologue Are 60S Ribosome Assembly Factors. Mol. Cell. Biol. 27: 2897-2909 [Abstract] [Full Text]  
  • Zavzavadjian, J. R., Couture, S., Park, W. S., Whalen, J., Lyon, S., Lee, G., Fung, E., Mi, Q., Liu, J., Wall, E., Santat, L., Dhandapani, K., Kivork, C., Driver, A., Zhu, X., Chang, M. S., Randhawa, B., Gehrig, E., Bryan, H., Verghese, M., Maer, A., Saunders, B., Ning, Y., Subramaniam, S., Meyer, T., Simon, M. I., O'Rourke, N., Chandy, G., Fraser, I. D. C. (2007). The Alliance for Cellular Signaling Plasmid Collection: A Flexible Resource for Protein Localization Studies and Signaling Pathway Analysis. Mol. Cell. Proteomics 6: 413-424 [Abstract] [Full Text]  
  • Kroemer, G., Galluzzi, L., Brenner, C. (2007). Mitochondrial Membrane Permeabilization in Cell Death. Physiol. Rev. 87: 99-163 [Abstract] [Full Text]  
  • Giroux, V., Iovanna, J., Dagorn, J.-C. (2006). Probing the human kinome for kinases involved in pancreatic cancer cell survival and gemcitabine resistance. FASEB J. 20: 1982-1991 [Abstract] [Full Text]  
  • Sastry, K. S. R., Smith, A. J., Karpova, Y., Datta, S. R., Kulik, G. (2006). Diverse Antiapoptotic Signaling Pathways Activated by Vasoactive Intestinal Polypeptide, Epidermal Growth Factor, and Phosphatidylinositol 3-Kinase in Prostate Cancer Cells Converge on BAD. J. Biol. Chem. 281: 20891-20901 [Abstract] [Full Text]  
  • Cotteret, S., Chernoff, J. (2006). Nucleocytoplasmic Shuttling of Pak5 Regulates Its Antiapoptotic Properties. Mol. Cell. Biol. 26: 3215-3230 [Abstract] [Full Text]  
  • Lin, Y., Kokontis, J., Tang, F., Godfrey, B., Liao, S., Lin, A., Chen, Y., Xiang, J. (2006). Androgen and its receptor promote bax-mediated apoptosis.. Mol. Cell. Biol. 26: 1908-1916 [Abstract] [Full Text]  
  • Belmonte, M. A., Santos, M. F., Kihara, A. H., Yan, C. Y. I., Hamassaki, D. E. (2006). Light-Induced Photoreceptor Degeneration in the Mouse Involves Activation of the Small GTPase Rac1.. IOVS 47: 1193-1200 [Abstract] [Full Text]  
  • Li, X., Minden, A. (2005). PAK4 Functions in Tumor Necrosis Factor (TNF) {alpha}-induced Survival Pathways by Facilitating TRADD Binding to the TNF Receptor. J. Biol. Chem. 280: 41192-41200 [Abstract] [Full Text]  
  • Matenia, D., Griesshaber, B., Li, X.-y., Thiessen, A., Johne, C., Jiao, J., Mandelkow, E., Mandelkow, E.-M. (2005). PAK5 Kinase Is an Inhibitor of MARK/Par-1, Which Leads to Stable Microtubules and Dynamic Actin. Mol. Biol. Cell 16: 4410-4422 [Abstract] [Full Text]  
  • Sunayama, J., Tsuruta, F., Masuyama, N., Gotoh, Y. (2005). JNK antagonizes Akt-mediated survival signals by phosphorylating 14-3-3. JCB 170: 295-304 [Abstract] [Full Text]  
  • Thiruchelvam, M., Prokopenko, O., Cory-Slechta, D. A., Richfield, E. K., Buckley, B., Mirochnitchenko, O. (2005). Overexpression of Superoxide Dismutase or Glutathione Peroxidase Protects against the Paraquat + Maneb-induced Parkinson Disease Phenotype. J. Biol. Chem. 280: 22530-22539 [Abstract] [Full Text]  
  • Hofmann, C., Shepelev, M., Chernoff, J. (2004). The genetics of Pak. J. Cell Sci. 117: 4343-4354 [Abstract] [Full Text]  
  • Zhang, B., Zhang, Y., Shacter, E. (2004). Rac1 Inhibits Apoptosis in Human Lymphoma Cells by Stimulating Bad Phosphorylation on Ser-75. Mol. Cell. Biol. 24: 6205-6214 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»