Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling.
Protein kinase C (PKC) is involved in a wide array of cellular processes such as cell proliferation, differentiation and apoptosis. Phosphorylation of both turn motif (TM) and hydrophobic motif (HM) are important for PKC function. Here, we show that the mammalian target of rapamycin complex 2 (mTORC2) has an important function in phosphorylation of both TM and HM in all conventional PKCs, novel PKCepsilon as well as Akt. Ablation of mTORC2 components (Rictor, Sin1 or mTOR) abolished phosphorylation on the TM of both PKCalpha and Akt and HM of Akt and decreased HM phosphorylation of PKCalpha. Interestingly, the mTORC2-dependent TM phosphorylation is essential for PKCalpha maturation, stability and signalling. Our study demonstrates that mTORC2 is involved in post-translational processing of PKC by facilitating TM and HM phosphorylation and reveals a novel function of mTORC2 in cellular regulation.
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Tsuneo
T
Ikenoue
Ken
K
Inoki
Qian
Q
Yang
Xiaoming
X
Zhou
Kun-Liang
KL
Guan
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D011494:Protein Kinases; C546843:mTOR protein, mouse; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C