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(Circulation Research. 2004;94:856.)
© 2004 American Heart Association, Inc.

Editorials

Aktion in the Nucleus

Keith A. Webster

From the Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Fla.

Correspondence to Keith A. Webster, Walter G. Ross Chair in Vascular Biology, Department of Molecular and Cellular Pharmacology, University of Miami Medical Center, 1600 NW 10th Ave, RMSB 6038, Miami, FL 33136. E-mail kwebster@chroma.med.miami.edu

Key Words: Akt • apoptosis • ischemia • gene therapy • Forkhead

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

Akt is a serine-threonine kinase first identified in mice as the cellular homologue of the v-akt oncogene and identified independently as a kinase related to protein kinases A and C.¹ As a consequence of the latter discoveries, Akt is also referred to as protein kinase B (PKB). There are three closely related mammalian Akts (Akt1/PKB, Akt 2/PKBß, and Akt 3/PKB) with similar substrate specificities but distinctive tissue distributions. They all share a common structure that consists of an N-terminal regulatory domain with pleckstrin homology (PH), a hinge region connecting the PH domain to the kinase domain, and a C-terminal region required for the induction and maintenance of the kinase activity. Akt sits strategically at the hub of insulin and insulin-like growth factor-1 (IGF-1) signaling, communicating directly with phosphatidylinositol 3-kinase (PI3-kinase) through the membrane lipids phosphatidylinositol 4,5 bisphosphate (PIP2) and phosphatidylinositol 3,4,5 triphosphate (PIP3). The pathway is also activated by growth factors including PDGFß, cytokines (leukemia inhibitory factor [LIF-1], and cardiotropin), and by adrenergic stimulation.^2,3 The src homology-2 (SH-2) domain-containing inositol phosphatase SHIP-1/2 and the PTEN phosphatase dephosphorylate Akt are critical mediators of the activity of the pathway.

Studies on the pro-oncogenic activities of Akt kinase first established its pivotal role in cell growth and survival. Akt was shown to promote transformation by suppressing apoptosis and differentiation and increasing cell cycle progression.¹ These activities were subsequently extended to nontumor cells including hematopoietic cells, neuronal cells, and cardiac myocytes, and Akt regulation is now being explored as a possible therapeutic . . . [Full Text of this Article]

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