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(Circulation Research. 2006;98:1349.)
© 2006 American Heart Association, Inc.

Editorials

Mission Impossible: IGF-1 and PTEN Specifically "Akt"ing on Cardiac L-Type Ca²⁺ Channels

Timothy J. Kamp, Nipavan Chiamvimonvat

From the Molecular and Cellular Arrhythmia Research Program (T.J.K.), Division of Cardiovascular Medicine, University of Wisconsin, Madison; the Division of Cardiovascular Medicine (N.C.), University of California, Davis; and the Department of Veterans Affairs (N.C.), Northern California Health Care System, Mather.

Correspondence to Dr Nipavan Chiamvimonvat, Division of Cardiovascular Medicine, University of California, One Shields Avenue, GBSF 6315, Davis, CA 95616. E-mail nchiamvimonvat@ucdavis.edu

See related article, pages 1390–1397

Key Words: cardiac L-type Ca²⁺ channels • phosphatidylinositol 3-kinase • insulin-like growth factor-1 • protein kinase Akt

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

The complex functional properties of cardiomyocytes are precisely regulated, oftentimes with millisecond precision. There are a multitude of signaling cascades and associated molecules that participate in this regulation. Insulin-like growth factor-1 (IGF-1), IGF receptors, phosphoinositides, phosphatidylinositol 3-kinase (PI3K), Akt or phosphokinase B (PKB), L-type Ca²⁺ channels (LTCC), and intracellular Ca²⁺ include some of the most studied and essential molecules governing many aspects of cardiac biology. In fact, it is difficult to name a cellular process in cardiomyocytes that is not in some way regulated by one or more of these molecules. This raises a fundamental question—is it possible for this group of diverse proteins and second messengers to work together, and yet provide the needed specificity in the cellular responses? The article by Sun et al in this issue of Circulation Research provides powerful evidence for a critical interface between cardiomyocyte Ca²⁺ signaling and PI3K-regulated pathways. Perhaps more importantly, the work begins to unravel some of the mystery behind the specificity of these seemingly diffuse pathways.¹

Rapid progress in recent years has provided strong evidence for the crucial role of a family of evolutionary conserved lipid kinases, PI3Ks, in mediating a wide range of cellular processes in response to stimulation by growth factors and hormones. This mediation sets in motion a coordinated series of events leading to cell growth, cell cycle entry, cell migration, and cell survival.^2,3 Various signaling proteins, including protein serine-threonine kinases, protein tyrosine kinases, and exchange factors that regulate heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins), have . . . [Full Text of this Article]

Related Article:

Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca²⁺ Currents via Increased PI3K/PKB Signaling

Hui Sun, Benoit-Gilles Kerfant, Dongling Zhao, Maria G. Trivieri, Gavin Y. Oudit, Josef M. Penninger, and Peter H. Backx
Circ. Res. 2006 98: 1390-1397. [Abstract] [Full Text] [PDF]

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