Molecular characterization of a cDNA encoding functional human CLK4 kinaseand localization to chromosome 4q35

Phosphorylated serine- and arginine-rich (SR) proteins play an important ro le in the formation of spliceosomes, possibly controlling the regulation of alternative splicing. Enzymes that phosphorylate the SR proteins belong to the family of CDC2/CDC28-like kinases (CLK). Employing nucleotide sequence comparison of human expressed sequence tag sequences to the murine counter part, we identified, cloned, and recombinantly expressed the human ortholog ue to the murine CLK4 cDNA. When fused to glutathione S-transferase, the ca talytically active human CLK4 is able to autophosphorylate and to phosphory late myelin basic protein, but not histone H2B as a substrate. Inspection o f mRNA accumulation demonstrated gene expression in all human tissues, with the most prominent abundance in liver, kidney, brain, and heart. Using flu orescence in situ hybridization, the human CLK4 cDNA was localized to band q35 on chromosome 4. (C) 2001 Academic Press.