This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Solski, P. A. Articles by Der, C. J. Search for Related Content PubMed PubMed Citation Articles by Solski, P. A. Articles by Der, C. J.

RhoA Biological Activity Is Dependent on Prenylation but Independent of Specific Isoprenoid Modification¹

University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Departments of Pharmacology [P. A. S., C. J. D.] and Microbiology and Immunology [W. H., L. S.], Chapel Hill, North Carolina 27599, and Department of Pharmacology, University of Wisconsin Medical School and Comprehensive Cancer Center, Madison, Wisconsin 53706 [P. J. K.]

Recent studies showed that specific isoprenoid modification may be critical for RhoB subcellular location and function. Therefore, we determined whether the function of the highly related RhoA protein is also critically dependent on specific isoprenoid modification: (a) in contrast to observations with RhoB or Ras proteins, where farnesylated and geranylgeranylated versions showed differences in subcellular location, both prenylated versions of RhoA showed the same plasma membrane and cytosolic location; (b) a farnesylated version of activated RhoA(63L) retained the same diverse functions as the normally geranylgeranylated RhoA(63L) protein, and both proteins show indistinguishable abilities to stimulate gene expression, cause growth transformation of NIH 3T3 mouse fibroblasts, to stimulate the motility of T47D human breast epithelial cells, and to block HIV-1 viral replication and gene expression; and (c) cells expressing farnesylated RhoA retained sensitivity to the growth inhibition caused by inhibition of geranylgeranyltransferase I, indicating that other proteins are critical targets for inhibitors of geranylgeranylation.

This article has been cited by other articles:

				A. M. Fontainhas and E. Townes-Anderson RhoA and Its Role in Synaptic Structural Plasticity of Isolated Salamander Photoreceptors Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 4177 - 4187. [Abstract] [Full Text] [PDF]

				C. A. Patel and S. Rattan RhoA Prenylation Inhibitor Produces Relaxation of Tonic Smooth Muscle of Internal Anal Sphincter J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 501 - 508. [Abstract] [Full Text] [PDF]

				E. J. Chenette, N. Y. Mitin, and C. J. Der Multiple Sequence Elements Facilitate Chp Rho GTPase Subcellular Location, Membrane Association, and Transforming Activity Mol. Biol. Cell, July 1, 2006; 17(7): 3108 - 3121. [Abstract] [Full Text] [PDF]

				A. C. Berzat, J. E. Buss, E. J. Chenette, C. A. Weinbaum, A. Shutes, C. J. Der, A. Minden, and A. D. Cox Transforming Activity of the Rho Family GTPase, Wrch-1, a Wnt-regulated Cdc42 Homolog, Is Dependent on a Novel Carboxyl-terminal Palmitoylation Motif J. Biol. Chem., September 23, 2005; 280(38): 33055 - 33065. [Abstract] [Full Text] [PDF]

				E. J. Chenette, A. Abo, and C. J. Der Critical and Distinct Roles of Amino- and Carboxyl-terminal Sequences in Regulation of the Biological Activity of the Chp Atypical Rho GTPase J. Biol. Chem., April 8, 2005; 280(14): 13784 - 13792. [Abstract] [Full Text] [PDF]

				P. A. Solski, R. S. Wilder, K. L. Rossman, J. Sondek, A. D. Cox, S. L. Campbell, and C. J. Der Requirement For C-terminal Sequences in Regulation of Ect2 Guanine Nucleotide Exchange Specificity and Transformation J. Biol. Chem., June 11, 2004; 279(24): 25226 - 25233. [Abstract] [Full Text] [PDF]

				N. Y. Mitin, M. B. Ramocki, A. J. Zullo, C. J. Der, S. F. Konieczny, and E. J. Taparowsky Identification and Characterization of Rain, a Novel Ras-interacting Protein with a Unique Subcellular Localization J. Biol. Chem., May 21, 2004; 279(21): 22353 - 22361. [Abstract] [Full Text] [PDF]

				K. Wennerberg and C. J. Der Rho-family GTPases: it's not only Rac and Rho (and I like it) J. Cell Sci., March 15, 2004; 117(8): 1301 - 1312. [Abstract] [Full Text] [PDF]

				P. L. Joyce and A. D. Cox Rac1 and Rac3 Are Targets for Geranylgeranyltransferase I Inhibitor-Mediated Inhibition of Signaling, Transformation, and Membrane Ruffling Cancer Res., November 15, 2003; 63(22): 7959 - 7967. [Abstract] [Full Text] [PDF]

				J. J. Fiordalisi, R. L. Johnson II, C. A. Weinbaum, K. Sakabe, Z. Chen, P. J. Casey, and A. D. Cox High Affinity for Farnesyltransferase and Alternative Prenylation Contribute Individually to K-Ras4B Resistance to Farnesyltransferase Inhibitors J. Biol. Chem., October 24, 2003; 278(43): 41718 - 41727. [Abstract] [Full Text] [PDF]