HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 22, 21483-21490, June 3, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/22/21483    most recent M500097200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yuan, Z.-q. Articles by Cheng, J. Q. Search for Related Content PubMed PubMed Citation Articles by Yuan, Z.-q. Articles by Cheng, J. Q. Social Bookmarking                      What's this?

ArgBP2 Interacts with Akt and p21-activated Kinase-1 and Promotes Cell Survival^*

Zeng-qiang Yuan, Donghwa Kim, Satoshi Kaneko, Melissa Sussman, Gary M. Bokoch¶, Gary D. Kruh**, Santo V. Nicosia, Joseph R. Testa**, and Jin Q. Cheng||

From the Departments of Pathology and Interdisciplinary Oncology, University of South Florida College of Medicine and H. Lee Moffitt Cancer Center, Tampa, Florida 33612, ^¶The Scripps Research Institute, La Jolla, California 92037, and ^**Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Akt/protein kinase B is a major cell survival pathway through phosphorylation of proapoptotic proteins Bad and Bax and of additional apoptotic pathways linked to Forkhead proteins glycogen synthase kinase-3 and ASK1. To further explore the mechanism by which Akt regulates cell survival, we identified an Akt interaction protein by yeast two-hybrid screening. It is highly homologous to ARG-binding protein 2 (ArgBP2) with splicing exon 8 of the coding region of the ArgBP2. As two splicing isoforms (ArgBP2 and -) of ArgBP2 have been identified (Wang, B., Golemis, E. A., and Kruh, G. D. (1997) J. Biol. Chem. 272, 17542–17550), it was named ArgBP2. ArgBP2 contains four Akt phosphorylation consensus sites, a SoHo motif, and three Src homology (SH) 3 domains and binds to C-terminal proline-rich motifs of Akt through its first and second SH3 domains. It also interacts with p21-activated protein kinase (PAK1) via its first and third SH3 domains, indicating the SH3 domains of ArgBP2 as docking sites for Akt and PAK1. Akt phosphorylates ArgBP2 in vitro and in vivo. Expression of ArgBP2 induces PAK1 activity and overrides apoptosis induced by ectopic expression of Bad or DNA damage. Nonphosphorylatable ArgBP2-4A and SH3 domain-truncated mutant ArgBP2 inhibit Akt-induced PAK1 activation and reduce Akt and PAK1 phosphorylation of Bad and antiapoptotic function. These data indicate that ArgBP2 is a physiological substrate of Akt, functions as an adaptor for Akt and PAK1, and plays a role in Akt/PAK1 cell survival pathway.

Received for publication, January 4, 2005 , and in revised form, March 2, 2005.

^* This work was supported by NCI, National Institutes of Health Grants CA77429, CA77935, CA89242, and CA107078 and Department of Defense Grants DAMD17-02-0671 and DAMD17-05-1-0021. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^|| To whom correspondence should be addressed: H. Lee Moffitt Cancer Center and Research Inst., SRB-3, 12902 Magnolia Dr., Tampa, FL 33612. Tel.: 813-745-6915; E-mail: ChengJQ{at}moffitt.usf.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. F. Franke Intracellular Signaling by Akt: Bound to Be Specific Sci. Signal., June 17, 2008; 1(24): pe29 - pe29. [Abstract] [Full Text] [PDF]

				D. Taieb, J. Roignot, F. Andre, S. Garcia, B. Masson, A. Pierres, J.-L. Iovanna, and P. Soubeyran ArgBP2-Dependent Signaling Regulates Pancreatic Cell Migration, Adhesion, and Tumorigenicity Cancer Res., June 15, 2008; 68(12): 4588 - 4596. [Abstract] [Full Text] [PDF]

				C. Burelout, P. H. Naccache, and S. G. Bourgoin Dissociation between the translocation and the activation of Akt in fMLP-stimulated human neutrophils--effect of prostaglandin E2 J. Leukoc. Biol., June 1, 2007; 81(6): 1523 - 1534. [Abstract] [Full Text] [PDF]

				C. Mestre-Escorihuela, F. Rubio-Moscardo, J. A. Richter, R. Siebert, J. Climent, V. Fresquet, E. Beltran, X. Agirre, I. Marugan, M. Marin, et al. Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas Blood, January 1, 2007; 109(1): 271 - 280. [Abstract] [Full Text] [PDF]

				G.-L. Zhou, D. F. Tucker, S. S. Bae, K. Bhatheja, M. J. Birnbaum, and J. Field Opposing Roles for Akt1 and Akt2 in Rac/Pak Signaling and Cell Migration J. Biol. Chem., November 24, 2006; 281(47): 36443 - 36453. [Abstract] [Full Text] [PDF]

				M. Mitsushima, K. Ueda, and N. Kioka Vinexin beta regulates the phosphorylation of epidermal growth factor receptor on the cell surface. Genes Cells, September 1, 2006; 11(9): 971 - 982. [Abstract] [Full Text] [PDF]