CLK (CDC-like Kinase) Family

Sino Biological provides a comprehensive set of tools for CLK family kinases related studies, including proteins, antibodies (rabbit mAbs, mouse mAbs, and rabbit pAbs), ELISA kits, and ORF cDNA clones. The CLK (CDC-like kinase) family kinases are an evolutionarily conserved group of dual specificity kinases, capable of phosphorylating protein substrates on serine, threonine, and tyrosine residues. The CLK family kinases are found in diverse species, from yeast to human. A critical role of the CLK family kinases is the regulation of mRNA splicing. They have shown to interact with, and phosphorylate, serine- and arginine-rich (SR) proteins of the spliceosomal complex, which is a part of the regulatory mechanism that enables the SR proteins to control RNA splicing. The CLK family kinases also participate in intracellular signal transduction cascades, and play important roles in development.

CLK Family Kinase Products

• CLK1
• CLK2
• CLK3

CLK Family Kinase Background

The CLK (CDC-like kinase) family kinases are an evolutionarily conserved group of dual specificity kinases, capable of phosphorylating protein substrates on serine, threonine, and tyrosine residues. The CLK family kinases are found in diverse species, including yeast, Drosophila, Arabidopsis, tobacco, mouse, rat, and human. A critical role for the CLK family kinases in development has been suggested by work on the Drosophila CLK homologue, DOA. Flies expressing low levels of the mutant DOA protein show marked neurologic abnormalities, and homozygosity for the DOA null allele is embryonically lethal.

Recent work on the murine CLK1 protein has begun to shed light on other physiological roles of the CLK family of kinases. Regulation of mRNA splicing is now recognized as a dynamic process, and one in which the CLK family of kinases may have an important function. CLK1 has been reported to bind to and phosphorylate serine/arginine-rich mRNA splicing factors on physiologically relevant sites in vitro. Moreover, Colwill et al.demonstrated that overexpression of CLK1 in COS cells leads to the subcellular redistribution of serine/ arginine-rich proteins, and to alterations in mRNA splicing in vivo. Collectively, these data strongly suggest a role for the CLK family kinases in the regulation of mRNA splicing in vivo.

The CLK family kinases may also participate in intracellular signal transduction cascades. Myers et al.showed that overexpression of CLK1 in the pheochromocytoma PC-12 cell line led to differentiation of these cells. Moreover, specific signal transduction intermediates were activated in these cells, including ERK1/2 and pp90^Rsk. Furthermore, immunocytochemical staining of 3T3 cells expressing human CLK3 demonstrated that the majority of immunoreactivity was present within the cytoplasm, and was less abundant in the nucleus. Similarly, staining of endogenous CLK1 in PC12 cells found it to be mostly cytoplasmic as well. In agreement with a putative signaling role for the CLK kinases is the finding that ethylene stimulation of tobacco leaves stimulates the activity of the tobacco CLK family member, PK12. These finding strongly suggest the existence of cytoplasmic targets for the CLK family kinases and their participation in intracellular signaling pathways.

CLK Family Kinase Related Studies

1. Myers M, et al. (1994) The dual-specificity CLK kinase induces neuronal differentiation of PC12 cells.
2. Duncan P, et al. (1997) In vivo regulation of alternative pre-mRNA splicing by the Clk1 protein kinase. Mol Cell Biol. 17(10): 5996–6001.
3. Duncan PI, et al. (1997) In vivo regulation of alternative pre-mRNA splicing by the Clk1 protein kinase. Mol Cell Biol. 17(10):5996-6001.
4. Moeslein FM. et al. (1999) The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. J Biol Chem. 274(38):26697-704.