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 Thr(256), is known to play a critical role in SGK1 activation. However, the identity of the protein kinase(s) responsible for phosphorylation of Ser(422), 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 Ser(422) phosphorylation as mTORC2 (mammalian target of rapamycin complex 2), a multiprotein kinase that phosphorylates a similar site in PKB (protein kinase B).
Yan
Lijun
L
Section of Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Mieulet
Virginie
V
Lamb
Richard F
RF
D020816:Amino Acid Motifs; D000818:Animals; D004789:Enzyme Activation; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases; C000631433:Pdk1 protein, mouse; C000631435:Pdk2 protein, mouse