The research plan proposes the characterization of intracellular mechanisms by which the cloned thrombin receptor mediates multiple cellular activities. Specifically, the candidate will: 1) identify G proteins which mediate thrombin signaling; 2) determine the functional sites for receptor-G protein interaction; and 3) define the cloned thrombin receptor's role in thrombin-induced activation of intracellular kinase cascades. These studies will allow the candidate to develop expertise in methodologies used to interrogate receptor-mediated signal transduction including: receptor expression in somatic cell and oocyte systems; chimeric receptor engineering; G protein binding assays; MAPK, Raf, and Ras activity assays; and the use of dominant negative mutants to explore the function of various signaling elements.
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| Ekelund, U E; Harrison, R W; Shokek, O et al. (1999) Intravenous allopurinol decreases myocardial oxygen consumption and increases mechanical efficiency in dogs with pacing-induced heart failure. Circ Res 85:437-45 |
| Hare, J M; Kim, B; Flavahan, N A et al. (1998) Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart. J Clin Invest 101:1424-31 |
| Hare, J M; Shernan, S K; Body, S C et al. (1997) Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance. Circulation 95:2250-3 |
