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(Circulation Research. 2006;99:339.)
© 2006 American Heart Association, Inc.

Editorials

Effects of Akt on Cardiac Myocytes

Location Counts

Daniele Catalucci, Gianluigi Condorelli

From the Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla; and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Multimedica, Milan, Italy.

Correspondence to Gianluigi Condorelli, Division of Cardiology, Department of Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0734. E-mail gcondorelli@ucsd.edu

See related article, pages 381–388

Key Words: Akt • stem cell • signaling • cardiomyocytes • hypertrophy

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

"Akt quisque ipse faber fortunae suae... " (Each Akt makes its own destiny....)

During the last few years, Akt (protein kinase B [PKB]) has become among the most studied signal-transduction molecules in cardiac biology. Akt is, in fact, at the crossroads of the insulin- and insulin-like growth factor-1 (IGF-1)–activated signal-transduction pathways. After insulin or IGF-1 interacts with its respective receptor, phosphatidylinositol 3-kinase (PI3K) phosphorylates inositol lipids that then bind to the pleckstrin domain of Akt, inducing its translocation to the plasma membrane. Here, Akt becomes the substrate of 3'-phosphoinositide-dependent kinase-1 (PDK-1), which activates it through phosphorylation of Thr308. Once active, Akt phosphorylates a number of "effector" substrates throughout the cell after migrating to subcellular organelles, including nuclei and mitochondria and other cytosolic locations. Therefore, the regulation of specific cellular functions is exerted by Akt at the level of the plasma membrane, nucleus, mitochondria, and cytosol in multiprotein complexes (Figure).

View larger version (40K): [in this window] [in a new window]   Binding of insulin (Ins) or IGF-1 activates PI3K and generates inositol lipids that bind to the pleckstrin domain of Akt, which is therefore localized to the plasma membrane where it becomes the substrate of PDK-1. Once activated, Akt migrates on plasma membrane itself, cytoplasm, mitochondria, and nucleus, phosphorylating key effector molecules. The result of this multitude of effects is improvement of metabolism, inotropism, and survival.

Models for studying the role of Akt, or its upstream molecules, in cardiac biology include cardiac-specific transgenic and knockout mice. Akt harboring mutations in either its pleckstrin or kinase domain, or containing . . . [Full Text of this Article]

Related Article:

Akt Promotes Increased Cardiomyocyte Cycling and Expansion of the Cardiac Progenitor Cell Population

Natalie Gude, John Muraski, Marta Rubio, Jan Kajstura, Erik Schaefer, Piero Anversa, and Mark A. Sussman
Circ. Res. 2006 99: 381-388. [Abstract] [Full Text] [PDF]

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