Editors' ChoiceSignal Integration

Highly Regulated Kinase

See allHide authors and affiliations

Science's STKE  27 Mar 2001:
Vol. 2001, Issue 75, pp. tw6
DOI: 10.1126/stke.2001.75.tw6

The serum- and glucocorticoid-induced protein kinase (Sgk) functions in regulation of transepithelial sodium transport in the kidney. Sodium transport is regulated by numerous hormones including aldosterone, vasopressin, and insulin. Sgk appears to contribute to such regulation as a point of convergence for various signals generated by the hormonal stiumui. As its name suggsts, expression of Sgk is regulated by serum, glucocorticoids, and aldosterone. But Sgk activity is also regulated posttranslationally, for example by insulin and insulin-like growth factors, in a manner that requires activation of phosphatidylinositol 3-kinase (PI3K) and the phosphoinositide-dependent protein kinases PDK-1 and PDK-2, which directly phosphorylate and activate Sgk. Perrotti et al. now report that Sgk is also a direct target for phosphorylation and activation by the cAMP-dependent protein kinase (PKA). Such activation of Sgk appears to require previous phosphorylation by one of the PDKs. The complex regulation of Sgk and its role in control of sodium transport suggest that it may be an important participant in control of hypertension that occurs with hyperinsulinemia and insulin resistance. Sgk is also found outside the kidney and could serve to integrate signals in other physiological processes as well.

N. Perrotti, R. A. He, S. A. Phillips, C. R. Haft, S. I. Taylor, Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. J. Biol. Chem. 276, 9406-9412 (2001). [Abstract] [Full Text]