AKT2 MESSENGER-RNA IS HIGHLY EXPRESSED IN EMBRYONIC BROWN FAT AND THEAKT2 KINASE IS ACTIVATED BY INSULIN

Akt2 encodes a protein-serine/threonine kinase containing a pleckstrin homology domain characteristic of many signaling molecules. Although there has been extensive interest in the mechanism by which the closel y-related Akt kinase participates in phosphatidylinositol S-kinase-med iated signaling, comparatively little is known regarding the expressio n and function of Akt2. This manuscript is the first to describe Akt2 mRNA expression in the developing mouse and the activation of AKT2 by insulin. These studies demonstrate that Akt2 is especially abundant in brown fat and, to a lesser extent, skeletal muscle and liver, tissues which are highly insulin-responsive and play a role in glucose metabo lism. Endogenous Akt2 expression also is upregulated in fully-differen tiated C2Cl2 myotubes and 3T3-L1 adipocytes, suggesting that these mur ine cell lines represent useful in vitro models for studies of Akt2 fu nction. We show that HA-tagged AKTZ is activated in response to insuli n stimulation in vitro and that activation of AKT2 is not induced in c ells pretreated with wortmannin, an inhibitor of phosphatidylinositol 3-kinase. These data suggest that Akr2 expression is fundamental to th e differentiated state of fat and muscle cells and that activation of AKT2 kinase by insulin is mediated through the phosphatidylinositol 3- kinase signaling pathway.