the transducer of regulated CREB protein 2 (TORC2) is a cAMP responsive coactivator that, in concert with LKB1 and AMPK, controls glucose homeostasis in the liver. Under fasting conditions, cytoplasmic TORC2 is transported to the nucleus where it binds to CREB and stimulates gluconeogenisis. Re-feeding and the ensuing insulin response inhibits gluconeogenic gene expression by promoting the phosphorylation, cytoplasmic export and degradation of TORC2. TORC2 is phosphorylated by the kinase QIK which in turn is activated by phosphorylation at Ser358 by insulin-activated Akt2. Phosphorylated TORC2 is subsequently ubiquitinylated at Lys 628 and degraded by the 26S proteasome. TORC2 protein levels and activity are increased in diabetes owing to a block in TORC2 phosphorylation, implicating this pathway in the pathogenesis of diabetes. The CREB/TORC2 regulatory axis controls the normal pattern of germinal center (GC) B cell gene activation/repression that promotes B cell development and circumvents GC lymphomagenesis. Note: This description may include information from UniProtKB.
Protein type: Transcription, coactivator/corepressor
Molecular Function: protein binding; cAMP response element binding protein binding; chromatin binding
Biological Process: transcription, DNA-dependent; viral reproduction; activation of CREB transcription factor; positive regulation of transcription from RNA polymerase II promoter; glucose homeostasis; gluconeogenesis; protein homotetramerization
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.