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

J. Biol. Chem., Vol. 279, Issue 16, 16441-16451, April 16, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/16/16441    most recent M312175200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahn, J.-Y. Articles by Ye, K. Search for Related Content PubMed PubMed Citation Articles by Ahn, J.-Y. Articles by Ye, K. Social Bookmarking                      What's this?

PIKE (Phosphatidylinositol 3-Kinase Enhancer)-A GTPase Stimulates Akt Activity and Mediates Cellular Invasion^*

Jee-Yin Ahn, Rong Rong, Todd G. Kroll, Erwin G. Van Meir, Solomon H. Snyder¶, and Keqiang Ye||

From the Department of Pathology and Laboratory Medicine, the Departments of Neurological Surgery and Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322 and the ^¶Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Akt/PKB is a crucial regulator of diverse cellular processes and contributes to cancer progression. Activation of Akt is essentially dependent on phosphatidylinositol (PI) 3-kinase signaling. Here, we describe a novel mediator of Akt that is independent of PI 3-kinase. This mediator, PIKE-A, is a PIKE isoform and contains GTPase, pleckstrin homology, ArfGAP, and ankyrin repeats domains. PIKE-A directly binds to activated Akt but not PI 3-kinase in a guanine nucleotide-dependent way and stimulates the kinase activity of Akt. Overexpression of PIKE-A enhances Akt activity and promotes cancer cell invasion, whereas dominant-negative PIKE-A and PIKE-A knockdown markedly inhibit these processes. Our results demonstrate that PIKE-A is a physiologic regulator of Akt and an oncogenic effector of cell invasion.

Received for publication, November 6, 2003 , and in revised form, February 3, 2004.

^* The work is supported by National Institutes of Health Grant RO1 NS045627 and The Sontag Foundation (to K. Y.). 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.

^|| To whom all correspondence should be addressed. Tel.: 404-712-2814; Fax: 404-712-2979; E-mail: kye{at}emory.edu.

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

This article has been cited by other articles:

				Y. Zhu, Y. Wu, J. I. Kim, Z. Wang, Y. Daaka, and Z. Nie Arf GTPase-activating Protein AGAP2 Regulates Focal Adhesion Kinase Activity and Focal Adhesion Remodeling J. Biol. Chem., May 15, 2009; 284(20): 13489 - 13496. [Abstract] [Full Text] [PDF]

				Y. Cai, J. Wang, R. Li, G. Ayala, M. Ittmann, and M. Liu GGAP2/PIKE-A Directly Activates Both the Akt and Nuclear Factor-{kappa}B Pathways and Promotes Prostate Cancer Progression Cancer Res., February 1, 2009; 69(3): 819 - 827. [Abstract] [Full Text] [PDF]

				R. Liu, B. Tian, M. Gearing, S. Hunter, K. Ye, and Z. Mao Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion PNAS, May 27, 2008; 105(21): 7570 - 7575. [Abstract] [Full Text] [PDF]

				E. J. Cuthbert, K. K. Davis, and J. E. Casanova Substrate specificities and activities of AZAP family Arf GAPs in vivo Am J Physiol Cell Physiol, January 1, 2008; 294(1): C263 - C270. [Abstract] [Full Text] [PDF]

				S. J. Werden, J. W. Barrett, G. Wang, M. M. Stanford, and G. McFadden M-T5, the Ankyrin Repeat, Host Range Protein of Myxoma Virus, Activates Akt and Can Be Functionally Replaced by Cellular PIKE-A J. Virol., March 1, 2007; 81(5): 2340 - 2348. [Abstract] [Full Text] [PDF]

				Y. Hu, Z. Liu, and K. Ye Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt signalings PNAS, November 15, 2005; 102(46): 16853 - 16858. [Abstract] [Full Text] [PDF]

				D. K. Scheidenhelm, J. Cresswell, C. A. Haipek, T. P. Fleming, R. W. Mercer, and D. H. Gutmann Akt-Dependent Cell Size Regulation by the Adhesion Molecule on Glia Occurs Independently of Phosphatidylinositol 3-Kinase and Rheb Signaling Mol. Cell. Biol., April 15, 2005; 25(8): 3151 - 3162. [Abstract] [Full Text] [PDF]

				A. Misra, M. Pellarin, J. Nigro, I. Smirnov, D. Moore, K. R. Lamborn, D. Pinkel, D. G. Albertson, and B. G. Feuerstein Array Comparative Genomic Hybridization Identifies Genetic Subgroups in Grade 4 Human Astrocytoma Clin. Cancer Res., April 15, 2005; 11(8): 2907 - 2918. [Abstract] [Full Text] [PDF]

				R. Rong, X. Tang, D. H. Gutmann, and K. Ye Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L PNAS, December 28, 2004; 101(52): 18200 - 18205. [Abstract] [Full Text] [PDF]