The renin-angiotensin system is a complex biochemical pathway that maintains homeostasis of blood pressure, blood volume and electrolyte composition. The active product of this pathway, angiotensin II, has effects on tissues throughout the body. Studies have demonstrated that virtually all of the physiologic actions of angiotensin II are mediated by the AT1 receptor. It is remarkable that angiotensin II binding to the identical receptor in the adrenal, the kidney, the liver and vascular smooth muscle cells causes such a diversity of tissue specific effects. This clearly suggests that the angiotensin II-AT1 receptor association is only the first step in a cascade of intracellular signals that progresses from the cell surface into the cytoplasm and the nucleus. It is these signals that stimulate tissue specific responses. Recently, it has become clear that tyrosine phosphorylation plays an important role in the early signalling responses mediated by angiotensin II. This grant is to study how angiotensin II, in binding to the seven-transmembrane AT1 receptor, stimulates the tyrosine phosphorylation of downstream kinases and heterotrimeric G-proteins in angiotensin II mediated tyrosine phosphorylation of phospholipase C, the JAK pathway and the Ras signaling pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044280-09
Application #
6150616
Study Section
General Medicine B Study Section (GMB)
Program Officer
Scherbenske, M James
Project Start
1992-02-01
Project End
2001-06-30
Budget Start
2000-02-01
Budget End
2001-06-30
Support Year
9
Fiscal Year
2000
Total Cost
$260,698
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Xiao, Hong D; Fuchs, Sebastien; Cole, Justin M et al. (2003) Role of bradykinin in angiotensin-converting enzyme knockout mice. Am J Physiol Heart Circ Physiol 284:H1969-77
Xiao, Hong D; Fuchs, Sebastien; Frenzel, Kristen et al. (2003) Newer approaches to genetic modeling in mice: tissue-specific protein expression as studied using angiotensin-converting enzyme (ACE). Am J Pathol 163:807-17
Cole, Justin M; Xiao, Hong; Adams, Jonathan W et al. (2003) New approaches to genetic manipulation of mice: tissue-specific expression of ACE. Am J Physiol Renal Physiol 284:F599-607

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