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SIK1A gene on chromosome 21q22.3 that encodes a serine/threonine-protein kinase involved in a plethora of cellular processes, including cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation, and tumour suppression. Once activated by by CaMK1, SIK1 regulates cognate proteins by phosphorylating them: it phosphorylates p53/TP53 in response to loss of adhesion thereby suppressing metastasis; it phosphorylates the PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of the sodium/potassium-transporting ATPase, ATP1A1, and subsequent increase of ATP1A1’s activity; and it phosphorylates muscle cells, inhibiting class-II histone deacetylases HDAC4 and HDAC5, thus promoting expression of MEF2 target genes in myocytes.
SIK1 is required during cardiomyogenesis, and regulates the exit of cardiomyoblasts from the cell cycle by downregulating CDKN1C/p57Kip2. SIK1 regulates hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators TORC1/CRTC1 and TORC2/CRTC2, inhibiting CREB activity; it also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1.
Defects in SIK1 are associated with breast and other cancers, and generally carry a poor prognosis.