SIK1 (F5D8F) Rabbit mAb #67776

Salt-inducible kinase 1 (SIK1) was originally identified as a serine/threonine kinase from adrenocortical tissues of rats on a high salt diet (1). SIK1 is an SNF1/AMPK family kinase capable of autophosphorylation (1). SIK2 is an isoform of SIK1 and is specifically expressed in adipose tissues where it is induced during adipocyte differentiation (2). Studies suggest that SIK2 can phosphorylate human insulin receptor substrate 1 (IRS-1) at Ser794. Along with evidence that SIK2 expression and activity are increased in white adipocytes of diabetic mice, this finding suggests a possible role for SIK2 in regulating insulin signaling in adipocytes and in the development of insulin resistance (2,3). Insulin triggers Akt2-mediated phosphorylation of SIK2 at Ser358 and the resultant kinase activation during post-fasting feeding (4). The activated SIK2 then induces the phosphorylation of TORC2 at Ser171, resulting in translocation of this transcriptional coactivator from the nucleus to the cytoplasm, where it is degraded through the ubiquitin pathway, leading to inhibition of gluconeogenic gene expression (4).