mTORC2 is the hydrophobic motif kinase for SGK1

The activation of the AGC (protein kinase A/protein kinase G/protein kinase C)-family kinase SGK1 (serum- and glucocorticoid-induced kinase 1) by insulin via PI3K (phosphoinositide 3-kinase) signalling has been appreciated for almost 10 years. PDK1 (phosphoinositide-dependent protein kinase 1), a kinase that phosphorylates the SGK1 catalytic domain at Thr²⁵⁶, is known to play a critical role in SGK1 activation. However, the identity of the protein kinase(s) responsible for phosphorylation of Ser⁴²², a site outside the catalytic domain (the so-called hydrophobic motif, or HM) that promotes activation of the kinase by PDK1, was unclear. In work reported in this issue of the Biochemical Journal, García-Martínez and Alessi have revealed the identity of a ‘PDK2’ kinase that catalyses Ser⁴²² phosphorylation as mTORC2 (mammalian target of rapamycin complex 2), a multiprotein kinase that phosphorylates a similar site in PKB (protein kinase B).