dual specificity protein kinase CLK2; CDC-like kinase 2 (CLK2)

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Function

dual specificity protein kinase
phosphorlates both Ser/Thr & Tyr-containing substrates
phosphorylates Ser- & Arg-rich (SR) proteins of the spliceosomal complex
may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing
role in redistribution of SR proteins from nuclear speckles to a diffuse nucleoplasmic distribution
acts as a suppressor of hepatic gluconeogenesis & glucose secretion by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation
phosphorylates PPP2R5B thus stimulating assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1
phosphorylates PTPN1, SRSF1 & SRSF3
regulates alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells
autophosphorylates on Ser, Thr & Tyr
phosphorylation on Ser-34 & Thr-127 by AKT1 is induced by ionizing radiation or insulin
phosphorylation plays a critical role in cell proliferation following low dose radiation & prevents cell death following high dose radiation
phosphorylation at Thr-344 by PKB/AKT2 induces its kinase activity which is required for its stability.
phosphorylation status at Ser-142 influences its subnuclear localization
- inhbition of phosphorylation at Ser-142 results in accumulation in nuclear speckles
interacts with RBMX
interacts with AKT1 & UBL5

Inhibition:

5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits CLK2 autophosphorylation
TG003 inhibits CLK2 kinase activity & affects the regulation of alternative splicing mediated by phosphorylation of SR proteins (putative)

belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, lammer subfamily
contains 1 protein kinase domain

isoform 1:
- nucleus, nuclear speckle
- inhbition of phosphorylation at Ser-142 results in accumulation in nuclear speckles (putative)
isoform 2:
- nuclear speckle
- colocalizes with Ser- & Arg-rich (SR) proteins in the nuclear speckles

named isoforms=3
at least one isoform lacks the kinase domain
at least one isoform may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay