Regulation of Protein Kinase B

Abstract

Protein kinase B (PKB) is a member of the second-messenger regulated subfamily of protein kinases implicated in signalling downstream of growth factor and insulin receptor tyrosine kinases and phosphatidylinositol 3-kinase (PI 3-kinase). PKB is activated by phosphorylation in response to mitogens and survival factors. Membrane recruitment driven by lipid second-messengers derived from PI 3-kinase leads to PKB phosphorylation and activation by upstream kinases (PDK1 and an as yet identified protein kinase). Prolonged stimulation with growth factors results in nuclear translocation, providing evidence that PKB activation at the plasma membrane precedes its nuclear translocation and supporting a role for PKB in signalling from receptor tyrosine kinases to the nucleus.