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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Survival kinases regulate cell death through the phosphorylation of comm...
Survival kinases regulate cell death through the phosphorylation of common substrates of the apoptotic machinery and cellular metabolism. PI3K generates PIP3, and PTEN converts PIP3 back to PIP2, negatively regulating PI3K signaling. PIP3 recruits PDK1, ILK, and Akt to the cell membrane. PDK1, ILK, and the rictor-mTOR complex are important for the activation of Akt. Expression of both SGK1 and Pim kinases is inducible. Akt, SGK1, and Pim kinases share common substrates of the apoptosis machinery and cellular metabolism, depicted as color-coded overlapping boxes (see text for full description). PFK2, phosphofructokinase-2.