Abstract:
:This study was undertaken to determine whether the response of smooth muscle cells to mitogens can be inhibited by inactivating ras with the ral GDS like protein-2 ras-binding domain (RGL2-RBD). RGL2 is a member of the ral GDS family of proteins that contains a carboxy terminal ras-binding domain which binds the GTP ligated form of ras and rap and a CDC25 homology domain with the structural features of a guanine nucleotide exchange factor. The effect of ras signaling on the smooth muscle cell growth factor response was studied using rat aortic A10 smooth muscle cells transfected with a plasmid that encoded the RGL2-RBD. RGL2-RBD transfection resulted in a 12-fold reduction in the number of clonal colonies that were obtained after selection, and dramatically slowed cell cycle progression. RGBL2-RBD reduced DNA synthesis and inhibited platelet derived growth factor (PDGF)-mediated activation of the MAPK pathway. These findings indicated that interfering with ras signaling inhibits smooth muscle cell proliferation and raise the possibility that ras signaling inhibition might be used therapeutically to control smooth muscle proliferation after vascular injury.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Fischer TH,Brittain J,Trabalzini L,Banes AJ,White GC,Smith CJ,Nichols TCdoi
10.1016/s0006-291x(03)00878-7subject
Has Abstractpub_date
2003-06-13 00:00:00pages
934-40issue
4eissn
0006-291Xissn
1090-2104pii
S0006291X03008787journal_volume
305pub_type
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