Disease relevance of Rgr

• These studies revealed that Rgr expression leads to the generation of various pathological alterations, including fibrosarcomas, when its transgenic expression is restricted to nonlymphoid tissues [1].
• More importantly, we also have demonstrated that Rgr expression in thymocytes of transgenic mice induces severe alterations in the development of the thymocytes, which eventually lead to a high incidence of thymic lymphomas [1].

High impact information on Rgr

• A photic visual cycle of rhodopsin regeneration is dependent on Rgr [2].
• Similarly, p15(INK4b)-deficient mouse embryo fibroblasts are more sensitive than wild-type cells to transformation by a combination of the Rgr and E1A oncogenes [3].
• In addition, Rgr reduced neurite outgrowth induced by a mutant Ras protein that preferentially activates Raf kinases [4].
• Elevation of Ral-GEF activity induced by transfection of a mutant Ras protein that preferentially activates Ral-GEFs, or by transfection of the catalytic domain of the Ral-GEF Rgr, suppressed cell cycle arrest and neurite outgrowth induced by nerve growth factor (NGF) treatment [4].
• These findings provide new insights into the tumorigenic role of Rgr as a potent oncogene and show that p15INK4b can act as a tumor suppressor gene [1].

Biological context of Rgr

• The effects of the 5'-truncated Rgr oncogene, a previously shown specific guanine exchange factor for Ral in vitro, in stimulating proliferation, cell transformation and gene expression were investigated [5].
• At the transcriptional level, Rgr enhances the activity of the serum response element and c-Jun [5].
• Rgr is 40% identical overall to Ral-GDS, with identity increasing to 72% over a 100 amino acid region of the catalytic domain [6].

Anatomical context of Rgr

• We have established TetRgr cell lines in which expression of Rgr can be inhibited by the presence of tetracycline in the medium [5].

Associations of Rgr with chemical compounds

• p190 RhoGAP is a tyrosine phosphorylated protein that contains an N-terminal GTP binding domain, a middle domain (MD) that mediates interaction with p120 RasGAP and a C-terminal GTPase-activating protein (GAP) domain that is specific for the &Rgr; family of small GTPases [7].

Other interactions of Rgr

• The retinal G protein-coupled receptor (RGR) is a protein that structurally resembles visual pigments and other G protein-coupled receptors [8].
• Additional analysis has shown that the activation of this pathway by Rgr is not due to a feed back mechanism mediated by the Grb2 adaptor protein [5].

References