CLK1 explained

Dual specificity protein kinase CLK1 is an enzyme that in humans is encoded by the CLK1 gene.^[1]

Function

This gene encodes a member of the CDC2-like (or LAMMER) family of dual specificity protein kinases. In the cell nucleus, the encoded protein phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing, releasing them into the nucleoplasm. The choice of splice sites during pre-mRNA processing may be regulated by the concentration of transacting factors, including serine/arginine-rich proteins. Therefore, the encoded protein may play an indirect role in governing splice site selection.^[2]

Interactions

CLK1 has been shown to interact with ASF/SF2.^{[3] [4]}

Further reading

• Johnson KW, Smith KA . Molecular cloning of a novel human cdc2/CDC28-like protein kinase. . J. Biol. Chem. . 266 . 6 . 3402–7 . 1991 . 10.1016/S0021-9258(19)67807-5 . 1704889 . free .
• Ben-David Y, Letwin K, Tannock L, Bernstein A, Pawson T . A mammalian protein kinase with potential for serine/threonine and tyrosine phosphorylation is related to cell cycle regulators . EMBO J. . 10 . 2 . 317–25 . 1991 . 1825055 . 452648 . 10.1002/j.1460-2075.1991.tb07952.x.
• Hanes J, von der Kammer H, Klaudiny J, Scheit KH . Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases . J. Mol. Biol. . 244 . 5 . 665–72 . 1995 . 7990150 . 10.1006/jmbi.1994.1763 .
• Colwill K, Pawson T, Andrews B, Prasad J, Manley JL, Bell JC, Duncan PI . The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution . EMBO J. . 15 . 2 . 265–75 . 1996 . 8617202 . 449941 . 10.1002/j.1460-2075.1996.tb00357.x.
• Colwill K, Feng LL, Yeakley JM, Gish GD, Cáceres JF, Pawson T, Fu XD . SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors . J. Biol. Chem. . 271 . 40 . 24569–75 . 1996 . 8798720 . 10.1074/jbc.271.40.24569 . free .
• Nestel FP, Colwill K, Harper S, Pawson T, Anderson SK . RS cyclophilins: identification of an NK-TR1-related cyclophilin . Gene . 180 . 1–2 . 151–5 . 1997 . 8973360 . 10.1016/S0378-1119(96)00436-2 .
• Moeslein FM, Myers MP, Landreth GE . The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B . J. Biol. Chem. . 274 . 38 . 26697–704 . 1999 . 10480872 . 10.1074/jbc.274.38.26697 . free .
• Menegay HJ, Myers MP, Moeslein FM, Landreth GE . Biochemical characterization and localization of the dual specificity kinase CLK1 . J. Cell Sci. . 113 . 18 . 3241–53 . 2000 . 10.1242/jcs.113.18.3241 . 10954422 .
• Kojima T, Zama T, Wada K, Onogi H, Hagiwara M . Cloning of human PRP4 reveals interaction with Clk1 . J. Biol. Chem. . 276 . 34 . 32247–56 . 2001 . 11418604 . 10.1074/jbc.M103790200 . free .
• Hartmann AM, Rujescu D, Giannakouros T, Nikolakaki E, Goedert M, Mandelkow EM, Gao QS, Andreadis A, Stamm S . Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors . Mol. Cell. Neurosci. . 18 . 1 . 80–90 . 2001 . 11461155 . 10.1006/mcne.2001.1000 . 18388526 .
• Lai MC, Lin RI, Tarn WY . Differential effects of hyperphosphorylation on splicing factor SRp55 . Biochem. J. . 371 . Pt 3 . 937–45 . 2003 . 12549978 . 1223332 . 10.1042/BJ20021827 .
• Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, Koizumi J, Hagiwara M, Ueda K . Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A . Biochem. Biophys. Res. Commun. . 301 . 2 . 324–9 . 2003 . 12565863 . 10.1016/S0006-291X(02)03017-6 .
• Kantham L, Kerr-Bayles L, Godde N, Quick M, Webb R, Sunderland T, Bond J, Walder K, Augert G, Collier G . Beacon interacts with cdc2/cdc28-like kinases . Biochem. Biophys. Res. Commun. . 304 . 1 . 125–9 . 2003 . 12705895 . 10.1016/S0006-291X(03)00549-7 .
• Prasad J, Manley JL . Regulation and Substrate Specificity of the SR Protein Kinase Clk/Sty . Mol. Cell. Biol. . 23 . 12 . 4139–49 . 2003 . 12773558 . 156123 . 10.1128/MCB.23.12.4139-4149.2003 .
• Hillman RT, Green RE, Brenner SE . An unappreciated role for RNA surveillance . Genome Biol. . 5 . 2 . R8 . 2005 . 14759258 . 395752 . 10.1186/gb-2004-5-2-r8 . free .
• Muraki M, Ohkawara B, Hosoya T, Onogi H, Koizumi J, Koizumi T, Sumi K, Yomoda J, Murray MV, Kimura H, Furuichi K, Shibuya H, Krainer AR, Suzuki M, Hagiwara M . Manipulation of alternative splicing by a newly developed inhibitor of Clks . J. Biol. Chem. . 279 . 23 . 24246–54 . 2004 . 15010457 . 10.1074/jbc.M314298200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Velazquez-Dones A, Hagopian JC, Ma CT, Zhong XY, Zhou H, Ghosh G, Fu XD, Adams JA . Mass spectrometric and kinetic analysis of ASF/SF2 phosphorylation by SRPK1 and Clk/Sty . J. Biol. Chem. . 280 . 50 . 41761–8 . 2006 . 16223727 . 10.1074/jbc.M504156200 . free .

Notes and References

1. Talmadge CB, Finkernagel S, Sumegi J, Sciorra L, Rabinow L . Chromosomal mapping of three human LAMMER protein-kinase-encoding genes . Hum Genet . 103 . 4 . 523–4 . Dec 1998 . 9856501 . 10.1007/s004390050861 . 40593571 .
2. Web site: Entrez Gene: CLK1 CDC-like kinase 1.
3. Colwill K, Feng LL, Yeakley JM, Gish GD, Cáceres JF, Pawson T, Fu XD . SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors . J. Biol. Chem. . 271 . 40 . 24569–75 . Oct 1996 . 8798720 . 10.1074/jbc.271.40.24569 . free .
4. Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, Koizumi J, Hagiwara M, Ueda K . Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A . Biochem. Biophys. Res. Commun. . 301 . 2 . 324–9 . Feb 2003 . 12565863 . 10.1016/S0006-291X(02)03017-6 .