The ras-binding domain of ral GDS-like protein-2 as a ras inhibitor in smooth muscle cells. Biochem Biophys Res Commun 2003 Jun 13;305(4):934-40
Date
05/28/2003Pubmed ID
12767920DOI
10.1016/s0006-291x(03)00878-7Scopus ID
2-s2.0-0037566754 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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.
Author List
Fischer TH, Brittain J, Trabalzini L, Banes AJ, White GC, Smith CJ, Nichols TCAuthor
Gilbert C. White MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBinding Sites
Cell Division
Cells, Cultured
Guanine Nucleotide Exchange Factors
MAP Kinase Signaling System
Mitogen-Activated Protein Kinases
Muscle, Smooth, Vascular
Platelet-Derived Growth Factor
Protein Structure, Tertiary
Proto-Oncogene Proteins p21(ras)
Rats
rab GTP-Binding Proteins
