CREB Regulated Transcription Coactivator 2 (CRTC2)

TORC2, a CREB coactivator. This module consisted of the calcium-regulated phosphatase calcineurin and the ser/thr kinase SIK2, both of which associated with TORC2. Under resting conditions, TORC2 was sequestered in the cytoplasm via a phosphorylation-dependent interaction with 14-3-3 proteins. Triggering of the calcium and cAMP second messenger pathways by glucose and gut hormones disrupted TORC2:14-3-3 complexes via complementary effects on TORC2 dephosphorylation; calcium influx increased calcineurin activity, whereas cAMP inhibited SIK2 kinase activity. The results illustrated how a phosphatase/kinase module connects 2 signaling pathways in response to nutrient and hormonal cues. TORC2 shares 32% amino acid identity with TORC1.