Document Detail


v-Src transformation is mediated through farnesylated proteins.
MedLine Citation:
PMID:  11469908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Src is an oncoprotein which has been implicated in a number of human malignancies in which it has been shown to be overexpressed and highly activated. The precise mechanism of Src transformation, however, is still poorly understood. We hypothesized that Ras and other farnesylated proteins may mediate Src transformation. To test this hypothesis, v-Src-transfected rat fibroblasts (3Y1) were treated every 72 h with a 15 microM concentration of a farnesyl-transferase inhibitor (FTI). At 2 weeks, a focus formation assay was performed to assess transformation potential. Untreated and FTI-treated v-Src-transfected 3Y1 cells formed a mean of 39 (+/-2.6) and 29.8 (+/-2.9) foci per well, respectively. This 24% decrease was judged to be statistically significant (P = 0.02). Moreover, foci (>90%) in the FTI-treated wells were also consistently smaller than foci in the untreated wells. Western blots with antibody directed toward H-Ras confirmed complete inhibition of Ras farnesylation in the treated cell lines. The specificity of this inhibition was verified by Western blot using antibody specific for Rap1A. The transforming potential of v-Src is inhibited, but not eliminated by FTI treatment. This suggests that v-Src transformation is mediated in part by farnesylated proteins, one of which may be Ras.
Authors:
S Teng; J Sun; R Irby; A D Hamilton; S Sebti; T J Yeatman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of surgical research     Volume:  99     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-07-25     Completed Date:  2001-08-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  343-6     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Department of Surgery, Ochsner Clinic and Hospital, New Orleans, Louisiana, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkyl and Aryl Transferases / antagonists & inhibitors,  metabolism*
Animals
Cell Line
Cell Transformation, Neoplastic / metabolism*
Enzyme Inhibitors / pharmacology
Farnesyltranstransferase
Fibroblasts / cytology
Oncogene Protein pp60(v-src) / genetics*
Rats
Transfection
rap1 GTP-Binding Proteins / metabolism
ras Proteins / metabolism
Grant Support
ID/Acronym/Agency:
K24 CA 85429-01/CA/NCI NIH HHS; UO1 CA85052-01A1/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.29/Farnesyltranstransferase; EC 2.7.10.2/Oncogene Protein pp60(v-src); EC 3.6.5.2/rap1 GTP-Binding Proteins; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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