The survival kinases Akt and Pim as potential pharmacological targets
Ravi Amaravadi, Craig B. Thompson
Ravi Amaravadi, Craig B. Thompson
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2618-2624. https://doi.org/10.1172/JCI26273.
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The survival kinases Akt and Pim as potential pharmacological targets

Abstract

The Akt and Pim kinases are cytoplasmic serine/threonine kinases that control programmed cell death by phosphorylating substrates that regulate both apoptosis and cellular metabolism. The PI3K-dependent activation of the Akt kinases and the JAK/STAT–dependent induction of the Pim kinases are examples of partially overlapping survival kinase pathways. Pharmacological manipulation of such kinases could have a major impact on the treatment of a wide variety of human diseases including cancer, inflammatory disorders, and ischemic diseases.

Authors

Ravi Amaravadi, Craig B. Thompson

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Figure 1

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Domain structure of the Akt and Pim kinases. The structures of human Akt...
Domain structure of the Akt and Pim kinases. The structures of human Akt1, Akt2, and Akt3 consist of a pleckstrin homology domain (PH) that binds to PIP3 at membrane surfaces, the kinase domain, and the regulatory domain. The 2 phosphorylation sites necessary for Akt activation are shown. The structures of human Pim-1, Pim-2, and Pim-3 demonstrate a conserved kinase domain and no regulatory domain. There are no required phosphorylation sites for Pim activation. Alternate start codons are depicted in Pim-2 leading to multiple Pim-2 isoforms that retain kinase activity.