he CDC-like protein kinases are a widespread family of splice factor kinases involved in normal physiology and in several diseases including cancer. In humans they include the CLK1, CLK2, CLK3 and CLK4 genes. The expression of CLK1 is regulated through alternative splicing producing both full-length catalytically active and truncated catalytically inactive isoforms, CLKT1 (arising from exon 4 skipping) and CLKT2 (arising from intron 4 retention). CLK kinases phosphorylate the so-called ‘SR protein’ splice factors, facilitating their activation and release from nuclear speckles. CLK kinases can also phosphorylate non-SR protein splice factors including the spliceosome-associated SPF45. CLK activity is increasingly associated with the development and progression of cancer.  As a result there is considerable interest in developing selective CLK inhibitors that block tumour growth. CLK1 is also a potential target in the treatment of Alzheimer's and has been earmarked for the treatment of Duchenne's muscular dystrophy as its inhibition causes the skipping of a mutated exon. CLK targeting has also been proposed for the treatment of viral infection including HIV-1 and influenza.


1.Dale P Corkery,et al. Nucleus. 2015; 6(4): 279–288.