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(Circulation Research. 2003;92:1059.)
© 2003 American Heart Association, Inc.

Editorials

Dissecting Cardiac Hypertrophy and Signaling Pathways

Evidence for an Interaction Between Multifunctional G Proteins and Prostanoids

Siiri E. Iismaa, Robert M. Graham

From the Molecular Cardiology Program, Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, New South Wales, Australia.

Correspondence to Robert M. Graham, FAA, MD, Victor Chang Cardiac Research Institute, 384 Victoria St, Darlinghurst, NSW 2010, Australia. E-mail b.graham@victorchang.unsw.edu.au

Key Words: prostanoids • tissue transglutaminase • cyclooxygenase • thromboxane • cardiac failure

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Over the past two decades, the ability to produce genetically engineered animal models has been widely used to unravel complex biological pathways involved in both physiology and disease. Although uniquely powerful and inherently elegant, these models, while often providing surprising new insights, have not uncommonly raised more questions than they have answered. A case in point is a transgenic mouse model developed to probe the in vivo role of the G protein, G_h, in cardiac signaling, and its consequences.¹ Unlike "traditional" heterotrimeric G proteins, G_h is decidedly atypical, being a multifunctional protein with both GTPase and transglutaminase (TGase) activity, and showing no sequence identity with other GTP-binding proteins. Moreover, although similar mouse models developed to study the role of G_q (a heterotrimeric G protein that, like G_h, mediates ₁-adrenergic receptor (₁-AR) signaling, as well as that by other Ca²⁺-mobilizing receptors) provided clear evidence for its critical involvement in pressure-overload hypertrophy via a mechanism involving protein kinase C (PKC) and phospholipase C (PLC) activation,^1,2 that for G_h demonstrated a mild form of hypertrophy by a mechanism that remained elusive. Evidence for PKC and PLC activation was lacking, and it was suggested, largely by default, that the hypertrophy in the cardiac G_h animals was due not to its signaling activity but to TGase-mediated protein crosslinking. In this issue of Circulation Research, FitzGerald and coworkers³ have reexamined this issue using an independently developed model of cardiac-restricted G_h overexpression. Interestingly, these studies provide evidence linking two major biological . . . [Full Text of this Article]

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				S. E. Iismaa, B. M. Mearns, L. Lorand, and R. M. Graham Transglutaminases and Disease: Lessons From Genetically Engineered Mouse Models and Inherited Disorders Physiol Rev, July 1, 2009; 89(3): 991 - 1023. [Abstract] [Full Text] [PDF]