عنوان
پدید آورنده
موضوع
رده
کتابخانه
محل استقرار
TLpq304458393
انگلیسی
The role of Rho proteins in transformation by G protein-coupled receptors
[Thesis]
I. E. Zohn
C. J. Der
The University of North Carolina at Chapel Hill
1998
140
Ph.D.
The University of North Carolina at Chapel Hill
1998
G protein-coupled receptors transduce extracellular signals from a wide variety of ligands to regulate a broad range of physiological responses. This family of cell surface receptors share a conserved predicted tertiary structure consisting of seven membrane spanning domains flanked by extracellular and intracellular loops. Upon ligand binding, G protein-coupled receptors activate heterotrimeric GTP-binding proteins (G-proteins) which regulate a variety of signal transduction pathways. The isolation of the mas oncogene provided the first indication that G protein-coupled receptors could behave as oncogenes. Since the isolation of Mas, a number of other G protein-coupled receptors and Gusd\alphausd-subunits have been shown to cause transformation of rodent fibroblasts. Additionally, G protein coupled receptors may also be involved in human tumor formation. The overall goal of my dissertation studies was to determine the mechanism of transformation by G protein-coupled receptors. G protein coupled receptors can activate a number of signal transduction pathways which may contribute to transformation. Both transforming G protein-coupled receptors and Gusd\alphausd subunits have been shown to activate Ras and Rho-dependent signal transduction pathways, and Ras and Rho proteins are involved in transformation by a number of different oncogenes. However, a role for activation of Ras and Rho in transformation by G protein-coupled receptor oncogenes was not demonstrated. We used three different transforming G protein-coupled receptors to investigate the mechanism of transformation of NIH 3T3 cells by G protein-coupled receptors: the mas oncogene, XGR and a turkey P2Y-purinergic receptor. Results from these studies suggest that activation of Rho family proteins is an essential mechanism of transformation by G protein-coupled receptors. Furthermore, these transforming G protein-coupled receptors exhibited two different mechanisms of transformation. Mas and the P2Y-purinergic receptor caused transformation by a Rac1-like mechanism, whereas XGR caused transformation by a RhoA-like mechanism. Finally, evidence is presented that the turkey P2Y-purinergic receptor and the mas oncogene cause transformation by coordinate activation of usd\rm G\alpha\sb{i}usd and usd\rm G\alpha\sb{q},usd whereas XGR causes transformation by activation of usd\rm G\alpha\sb.usd These results suggest that Rho proteins maybe an effective anti-cancer drug target for tumors which have up regulated activity of G protein-coupled receptors.
Biological sciences
G protein-coupled receptors
Pure sciences
Rho proteins
Signal transduction
Transformation
C. J. Der
I. E. Zohn
مطالعه متن کتاب p
[Thesis]
276903
a
Y
