Akt/PKB is a key master regulator of a wide range of physiological functions including metabolism, proliferation, survival, growth, angiogenesis and migration and invasion. The Akt protein kinase family comprises three highly related isoforms encoded by different genes. The initial observation that the Akt isoforms share upstream activators as well as several downstream effectors, together with the high sequence homology suggested that their functions were mostly redundant. By contrast, an increasing body of evidence has recently uncovered the concept of Akt isoform signaling specificity, supported by distinct phenotypes displayed by animal strains genetically modified for each of the three genes, as well as by the identification of isoform-specific substrates and association with discrete subcellular locations. Given that Akt is regarded as a promising therapeutic target in a number of pathologies, it is essential to dissect the relative contributions of each isoform, as well as the degree of compensation in pathophysiological function. Here we summarize our view of how Akt selectivity is achieved in the context of subcellular localization, isoform-specific substrate phosphorylation and context-dependent functions in normal and pathophysiological settings.

Signaling specificity in the Akt pathway in biology and disease / Toker, Alex; Marmiroli, Sandra. - In: ADVANCES IN BIOLOGICAL REGULATION. - ISSN 2212-4926. - 55:(2014), pp. 28-38-38. [10.1016/j.jbior.2014.04.001]

Signaling specificity in the Akt pathway in biology and disease

MARMIROLI, Sandra
2014

Abstract

Akt/PKB is a key master regulator of a wide range of physiological functions including metabolism, proliferation, survival, growth, angiogenesis and migration and invasion. The Akt protein kinase family comprises three highly related isoforms encoded by different genes. The initial observation that the Akt isoforms share upstream activators as well as several downstream effectors, together with the high sequence homology suggested that their functions were mostly redundant. By contrast, an increasing body of evidence has recently uncovered the concept of Akt isoform signaling specificity, supported by distinct phenotypes displayed by animal strains genetically modified for each of the three genes, as well as by the identification of isoform-specific substrates and association with discrete subcellular locations. Given that Akt is regarded as a promising therapeutic target in a number of pathologies, it is essential to dissect the relative contributions of each isoform, as well as the degree of compensation in pathophysiological function. Here we summarize our view of how Akt selectivity is achieved in the context of subcellular localization, isoform-specific substrate phosphorylation and context-dependent functions in normal and pathophysiological settings.
2014
55
28-38
38
Signaling specificity in the Akt pathway in biology and disease / Toker, Alex; Marmiroli, Sandra. - In: ADVANCES IN BIOLOGICAL REGULATION. - ISSN 2212-4926. - 55:(2014), pp. 28-38-38. [10.1016/j.jbior.2014.04.001]
Toker, Alex; Marmiroli, Sandra
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1066009
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