Disease relevance of Rhoq

• Treatments of differentiated adipocytes with latrunculin B, Clostridium difficile toxin B or a dominant-interfering TC10 mutant (TC10/T31N) disrupted the Cav-actin structure without significantly affecting the organization of clustered caveolae [1].
• In conclusion, our data demonstrate that Cbl/CAP/TC10 insulin signaling pathway is active in cardiac muscle and impaired during obesity and insulin deficiency [2].

High impact information on Rhoq

• The activation of TC10 is essential for insulin-stimulated glucose uptake and GLUT4 translocation [3].
• Together, these data demonstrate that PKCzeta/lambda can serve as a convergent downstream target for both the PI 3-kinase and TC10 signaling pathways, but only the TC10 pathway induces a spatially restricted targeting to the plasma membrane [4].
• In parallel, insulin stimulation as well as TC10/Q75L resulted in the activation loop phosphorylation of PKCzeta [4].
• Insulin induces phosphatidylinositol-3-phosphate formation through TC10 activation [5].
• These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways [6].

Biological context of Rhoq

• CONCLUSIONS: TC10 possesses distinct features, but exhibits a phenotype most closely related to that of Cdc42 [7].
• Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor-mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10 [6].
• Subsequent TC10 activation was detected only in heart and adipose tissue. c-Cbl and CAP gene expression was significantly reduced in the heart tissue of streptozotocin-induced diabetic animals, whereas no change was observed for other components of the pathway [2].

Anatomical context of Rhoq

• TC10 mRNA was most highly expressed in heart and skeletal muscle [7].
• RESULTS: A gain-of-function TC10 mutant protein expressed in fibroblasts induced cell rounding, loss of stress fibers and formation of peripheral extensions [7].
• Thus, N-WASP is essential for the process formation and neurite outgrowth induced by Tc10 and RhoT [8].
• TC10 alpha and beta-transcripts are amplified by RT-PCR in muscle cells, but the endogenous proteins are barely detectable using two unrelated antibodies [9].
• TC10 alpha transfected into myoblasts is activated by insulin despite the lack of CAP expression and Cbl phosphorylation [9].

Associations of Rhoq with chemical compounds

• A Crk-II/TC10 signaling pathway is required for osmotic shock-stimulated glucose transport [10].
• Tc10 was highly expressed in muscular tissues and brain and remarkably induced during differentiation of C2 skeletal muscle cells and neuronal differentiation of PC12 and N1E-115 cells [8].
• Neuronal differentiation of PC12 and N1E-115 cells induced by dibutyryl cyclic AMP and by serum starvation, respectively, was prevented by dominant-negative Cdc42, Tc10 and RhoT [8].

Other interactions of Rhoq

• These data provide the first evidence that activation of TC10 and remodeling of cortical actin, which could occur through the TC10 signaling, are required for osmotic shock-mediated Glut 4 translocation and glucose uptake [10].

Analytical, diagnostic and therapeutic context of Rhoq

• After oral administration of TC 10 mg/kg body wt/day to mice 7 days prior to whole body irradiation (8 Gy) there was no mortality until day 13 and 50% of the animals survived until day 30 [11].

References