Volume 2, Number 1, March 2001

Signal transduction mechanisms of the angiotensin II type AT₁-receptor: looking beyond the heterotrimeric G protein paradigm
Peter P Sayeski, Kenneth E Bernstein

Angiotensin II (Ang II) is the effector molecule of the renin-angiotensin-aldosterone system (RAAS). This small peptide binds cell surface receptors to maintain a wide variety of haemodynamic responses including salt and water balance, blood pressure and vascular tone. Ang II can also act as a potent growth factor. Under certain conditions however, its growth-promoting effects can be deleterious and lead to vascular disease. The intracellular signalling mechanisms by which the Ang II type 1 (AT₁) receptor converts ligand binding to the appropriate cellular response are the focus of this review. Here, the classical signalling pathway utilising heterotrimeric G proteins is discussed. In addition, more recent work examining the role of tyrosine phosphorylation signalling cascades is also examined. Defining the biochemical signalling pathways by which Ang II mediates its physiological effects will advance our understanding of how such a simple molecule elicits such a wide variety of important cellular responses. Furthermore, it may delineate the mechanisms by which Ang II generates a normal vs. an abnormal cellular response, the results of which lead to vascular disease states that are routinely seen in humans.

JRAAS 2001;2:4-10.

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