JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M208896200 on January 23, 2003

J. Biol. Chem., Vol. 278, Issue 15, 13207-13215, April 11, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/15/13207    most recent
M208896200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, X.
Right arrow Articles by Liu, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, X.
Right arrow Articles by Liu, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

A Rac/Cdc42-specific Exchange Factor, GEFT, Induces Cell Proliferation, Transformation, and Migration*

Xiangrong GuoDagger §, Lewis Joe StaffordDagger , Brad BryanDagger , Chunzhi XiaDagger , Wenbin MaDagger , Xiushan Wu§, Dan Liu, Zhou Songyang, and Mingyao LiuDagger §||

From the Dagger  Center for Cancer Biology and Nutrition, Alkek Institute of Biosciences and Technology, and Department of Medical Biochemistry and Genetics, Texas A&M University System Health Science Center, Houston, Texas 77030, the § College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, People's Republic of China, and the  Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030

The Rho family of small GTPases, including Rho, Rac, and Cdc42, play essential roles in diverse cellular functions. The ability of Rho family GTPases to participate in signaling events is determined by the ratio of inactive (GDP-bound) and active (GTP-bound) forms in the cell. The activation of Rho family proteins requires the exchange of bound GDP for GTP, a process catalyzed by the Dbl family of guanine nucleotide exchange factors (GEFs). The GEFs have high affinity for the guanine nucleotide-free state of the GTPases and are thought to promote GDP release by stabilizing an intermediate transition state. In this study, we have identified and characterized a new Rac/Cdc42-specific Dbl family guanine nucleotide exchange factor, named GEFT. GEFT is highly expressed in the excitable tissues, including brain, heart, and muscle. Low or very little expression was detected in other nonexcitable tissues. GEFT has specific exchange activity for Rac and Cdc42 in our in vitro GTPase exchange assays and glutathione S-transferase-PAK pull-down assays with GTP-bound Rac1 and Cdc42. Overexpression of GEFT leads to changes in cell morphology and actin cytoskeleton re-organization, including the formation of membrane microspikes, filopodia, and lamilliopodia. Furthermore, expression of GEFT in NIH3T3 cells promotes foci formation, cell proliferation, and cell migration, possibly through the activation of transcriptional factors involved in cell growth and proliferation. Together, our data suggest that GEFT is a Rac/Cdc42-specific GEF protein that regulates cell morphology, cell proliferation, and transformation.

* This work was supported in part by NHLBI National Institutes of Health Grant 5R01 HL64792 and a grant from the Department of Defense (to M. L.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF4487514 for human and AF4487515 for mouse.

|| Basil O'Conner Scholar of the March of Dimes Foundation. To whom correspondence should be addressed: Center for Cancer Biology and Nutrition, Alkek Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 Holcombe Blvd., Houston, TX 77030. Tel.: 713-677-7505; Fax: 713-677-7512; E-mail: mliu@ibt.tamu.edu.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
T. K. Smith, H. A. Hager, R. Francis, D. M. Kilkenny, C. W. Lo, and D. M. Bader
Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity
PNAS, June 17, 2008; 105(24): 8298 - 8303.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. J. Rojas, M. E. Yohe, S. Gershburg, T. Kawano, T. Kozasa, and J. Sondek
G{alpha}q Directly Activates p63RhoGEF and Trio via a Conserved Extension of the Dbl Homology-associated Pleckstrin Homology Domain
J. Biol. Chem., October 5, 2007; 282(40): 29201 - 29210.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
M. Kedmi and A. Orr-Urtreger
Differential brain transcriptome of {beta}4 nAChR subunit-deficient mice: is it the effect of the null mutation or the background strain?
Physiol Genomics, January 17, 2007; 28(2): 213 - 222.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
L. Vidali, F. Chen, G. Cicchetti, Y. Ohta, and D. J. Kwiatkowski
Rac1-null Mouse Embryonic Fibroblasts Are Motile and Respond to Platelet-derived Growth Factor
Mol. Biol. Cell, May 1, 2006; 17(5): 2377 - 2390.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
B. A. Bryan, D. C. Mitchell, L. Zhao, W. Ma, L. J. Stafford, B.-B. Teng, and M. Liu
Modulation of Muscle Regeneration, Myogenesis, and Adipogenesis by the Rho Family Guanine Nucleotide Exchange Factor GEFT
Mol. Cell. Biol., December 15, 2005; 25(24): 11089 - 11101.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Bioactive and Compatible PolymersHome page
M. Mattioli-Belmonte, G. Biagini, G. Lucarini, L. Virgili, F. Gabbanelli, S. Amati, F. Cecchet, A.-C. Albertsson, A. Finne, and N. Andronova
Suitable Materials for Soft Tissue Reconstruction: In Vitro Studies of Cell - Triblock Copolymer Interactions
Journal of Bioactive and Compatible Polymers, November 1, 2005; 20(6): 509 - 526.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
M. Bredel, C. Bredel, D. Juric, G. R. Harsh, H. Vogel, L. D. Recht, and B. I. Sikic
High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors
Cancer Res., May 15, 2005; 65(10): 4088 - 4096.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
C. A. Rabiner, R. E. Mains, and B. A. Eipper
Kalirin: A Dual Rho Guanine Nucleotide Exchange Factor That Is So Much More Than the Sum of Its Many Parts
Neuroscientist, April 1, 2005; 11(2): 148 - 160.
[Abstract] [PDF]

Home page
 J. Biol. Chem.Home page
M. Lee, M. Hadi, G. Hallden, and G. W. Aponte
Peptide YY and Neuropeptide Y Induce Villin Expression, Reduce Adhesion, and Enhance Migration in Small Intestinal Cells through the Regulation of CD63, Matrix Metalloproteinase-3, and Cdc42 Activity
J. Biol. Chem., January 7, 2005; 280(1): 125 - 136.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Bryan, V. Kumar, L. J. Stafford, Y. Cai, G. Wu, and M. Liu
GEFT, A Rho Family Guanine Nucleotide Exchange Factor, Regulates Neurite Outgrowth and Dendritic Spine Formation
J. Biol. Chem., October 29, 2004; 279(44): 45824 - 45832.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Davidson, A. J. Pawson, R. P. Millar, and S. Maudsley
Cytoskeletal Reorganization Dependence of Signaling by the Gonadotropin-releasing Hormone Receptor
J. Biol. Chem., January 16, 2004; 279(3): 1980 - 1993.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. H. Amin, H.-Q. Chen, R. Veluthakal, R. B. Silver, J. Li, G. Li, and A. Kowluru
Mastoparan-Induced Insulin Secretion from Insulin-Secreting {beta}TC3 and INS-1 Cells: Evidence for Its Regulation by Rho Subfamily of G Proteins
Endocrinology, October 1, 2003; 144(10): 4508 - 4518.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.