RhoA biological activity is dependent on prenylation but independent of specific isoprenoid modification.
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.
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Departments of Pharmacology, Chapel Hill, North Carolina 27599, USA.
Patricia A
PA
Solski
Whitney
W
Helms
Patricia J
PJ
Keely
Lishan
L
Su
Channing J
CJ
Der
D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D051231:Farnesyltranstransferase; D015497:HIV-1 / Q000254:growth & development; D051379:Mice; D016296:Mutagenesis / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics; D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D017368:Protein Prenylation; D026362:Serum Response Factor / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D014779:Virus Replication / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism
D016328:NF-kappa B; D011106:Polyisoprenyl Phosphates; D026362:Serum Response Factor; D019938:Cyclin D1; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein