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(Circulation Research. 2001;88:975.)
© 2001 American Heart Association, Inc.

Editorial

Akt Like a Woman

Gender Differences in Susceptibility to Cardiovascular Disease

Peter H. Sugden, Angela Clerk

From the Cardiac Medicine Section, National Heart and Lung Institute Division (P.H.S.) and the Cell and Molecular Biology Section, Biomedical Sciences Division (A.C.), Imperial College School of Medicine, London, UK.

Correspondence to Peter H. Sugden, National Heart and Lung Institute Division (Cardiac Medicine Section), Imperial College School of Medicine, Dovehouse St, London SW3 6LY, UK. E-mail p.sugden@ic.ac.uk

Key Words: Akt • gender • estrogen • cardiac myocytes • apoptosis

	Introduction

 
The oncogenic murine AKT8 retrovirus was identified almost 25 years ago, and the presence of the causative oncogenic agent v-akt was subsequently demonstrated in transformed cells or tumors from both mice and humans.^{1 2} The cellular homolog of v-akt was cloned in the early 1990s and was termed c-Akt (or simply Akt). Largely on the basis of its sequence similarity to both protein kinases A and C, it was concluded that Akt (alternatively known as protein kinase B [PKB]) represented a Ser-/Thr- protein kinase. Three mammalian genes have been identified, with transcripts of akt1 and akt2 being highly expressed in heart. The explosion of interest in Akt was the direct consequence of the realization that it is an effector of the lipid signaling molecule phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P₃] (Figure).

View larger version (18K): [in this window] [in a new window]   Figure 1. Possible actions of Akt in the cardiovascular system. Arrows indicate activation; bars indicate inhibition. Phosphorylation of Bad inhibits its proapoptic activity by reducing its inhibition of the antiapoptotic actions of Bcl-2 and Bcl-XL. The overall consequences of activation of Akt are shown in boxes. For additional explanation, see the text. PDK indicates PtdIns(3,4,5)P3-dependent kinase; eNOS, endothelial NO synthase.

By binding to their transmembrane receptor protein tyrosine kinases, a variety of growth factors, including insulin and insulin-like growth factor 1 (IGF1), activate the lipid kinase phosphatidylinositol 3-kinase (PI3K) to phosphorylate the membrane phospholipid PtdIns(4,5)P₂, producing PtdIns(3,4,5)P₃. PtdIns(3,4,5)P₃ remains in the plane of the membrane and may serve to recruit Akt to this compartment from its normal . . . [Full Text of this Article]

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