Figure 4. Physiological roles of different SIK isoforms identified by genetic analysis.

The contribution of individual SIK isoforms to the regulation of physiological processes identified by the use of knock-out and/or knock-in mice. The major SIK isoform/s responsible for each role is colour coded; SIK1 (red), SIK2 (blue), SIK3 (green), SIK2 and SIK3 (purple). (SIKs) The SIKs have a role in modulating gluconeogenesis in mouse hepatocytes, but which SIK isoform(s) is responsible is unknown. In humans, mutations in SIK1 have been identified in patients with early-onset epilepsy. Consistent with the role in bone formation, a point mutation in SIK3 has been identified in a human patient with skeletal defects.