High impact information on SNF1LK2

• This module consists of the calcium-regulated phosphatase calcineurin and the Ser/Thr kinase SIK2, both of which associate with TORC2 [1].
• Adenovirus-mediated overexpression of SIK2 in adipocytes elevated the level of phosphorylation at Ser(789), the mouse equivalent of human Ser(794) [2].
• SIK2 was specifically expressed in adipose tissues [2].
• When 3T3-L1 cells were treated with the adipose differentiation mixture, SIK2 mRNA was induced within 1 h, the time of induction almost coinciding with that of c/EBPbeta mRNA [2].
• SIK2 is found in adipocytes and phosphorylates a specific serine residue in insulin receptor substrate-1 [3].

Biological context of SNF1LK2

• Triggering of the calcium and cAMP second messenger pathways by glucose and gut hormones disrupts TORC2:14-3-3 complexes via complementary effects on TORC2 dephosphorylation; calcium influx increases calcineurin activity, whereas cAMP inhibits SIK2 kinase activity [1].
• These results strongly suggest that SIK2 may play important role(s) in modulating the insulin-signaling cascade of adipocytes, and thus, may be involved in the development of insulin resistance [4].
• The SIK2 gene was expressed in 3T3-L1 cells at a very early stage of adipogenesis [4].

Anatomical context of SNF1LK2

• The cloning of salt-inducible kinase-1 (SIK1) that was specifically expressed in the adrenal glands of high-salt diet-fed rats led to subsequent cloning of adipose-specific SIK2 and rather ubiquitous SIK3 [4].

Regulatory relationships of SNF1LK2

• The expression and/or activity of several kinases, such as IkappaB kinase beta (IKKbeta) and salt-induced kinase 2 (SIK2), and the phosphorylation of IRS-1 at key sites, such as Ser307 and Ser789, are increased in states of insulin resistance [5].

References