Dual specificity protein kinase

Function

Dual specificity protein kinases are kinases which act as both tyrosine kinase and serine/threonine kinase.

CLK1 phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing.
Clk2 and Clk3 cause the redistribution of SR proteins and can regulate the alternative splicing of precursor mRNA^[1].
CLK4 phosphorylates tyrosine or serine/threonine^[2].

Structural highlights

The dual specificity protein kinase TTK or monopolar spindle kinase 1 contains tetratricopeptide repeat domain (TPR) which serves as interaction domain between proteins. The TPR domain is a helical 34 amino acid motif which is found in several copies in a protein which fold together forming a protein-protein binding domain. Cancer therapy potential drugs bind in .^[3]^[4]

3D structures of dual specificity protein kinase

Dual specificity protein kinase 3D structures

Dual specificity protein kinase TTK kinase domain complex with inhibitor, 2x9e

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Duncan PI, Stojdl DF, Marius RM, Scheit KH, Bell JC. The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing. Exp Cell Res. 1998 Jun 15;241(2):300-8. PMID:9637771 doi:http://dx.doi.org/S0014-4827(98)94083-6
↑ Shen Y, Zhang H, Yao S, Su F, Wang H, Yin J, Fang Y, Tan L, Zhang K, Fan X, Zhong M, Zhou Q, He J, Zhang Z. Methionine oxidation of CLK4 promotes the metabolic switch and redox homeostasis in esophageal carcinoma via inhibiting MITF selective autophagy. Clin Transl Med. 2022 Jan;12(1):e719. PMID:35092699 doi:10.1002/ctm2.719
↑ Dhanasekaran N, Premkumar Reddy E. Signaling by dual specificity kinases. Oncogene. 1998 Sep 17;17(11 Reviews):1447-55. PMID:9779990 doi:http://dx.doi.org/10.1038/sj.onc.1202251
↑ Colombo R, Caldarelli M, Mennecozzi M, Giorgini ML, Sola F, Cappella P, Perrera C, Depaolini SR, Rusconi L, Cucchi U, Avanzi N, Bertrand JA, Bossi RT, Pesenti E, Galvani A, Isacchi A, Colotta F, Donati D, Moll J. Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase. Cancer Res. 2010 Dec 15;70(24):10255-64. PMID:21159646 doi:10.1158/0008-5472.CAN-10-2101

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Duncan PI, Stojdl DF, Marius RM, Scheit KH, Bell JC. The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing. Exp Cell Res. 1998 Jun 15;241(2):300-8. PMID:9637771 doi:http://dx.doi.org/S0014-4827(98)94083-6

[2] Shen Y, Zhang H, Yao S, Su F, Wang H, Yin J, Fang Y, Tan L, Zhang K, Fan X, Zhong M, Zhou Q, He J, Zhang Z. Methionine oxidation of CLK4 promotes the metabolic switch and redox homeostasis in esophageal carcinoma via inhibiting MITF selective autophagy. Clin Transl Med. 2022 Jan;12(1):e719. PMID:35092699 doi:10.1002/ctm2.719

[3] Dhanasekaran N, Premkumar Reddy E. Signaling by dual specificity kinases. Oncogene. 1998 Sep 17;17(11 Reviews):1447-55. PMID:9779990 doi:http://dx.doi.org/10.1038/sj.onc.1202251

[4] Colombo R, Caldarelli M, Mennecozzi M, Giorgini ML, Sola F, Cappella P, Perrera C, Depaolini SR, Rusconi L, Cucchi U, Avanzi N, Bertrand JA, Bossi RT, Pesenti E, Galvani A, Isacchi A, Colotta F, Donati D, Moll J. Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase. Cancer Res. 2010 Dec 15;70(24):10255-64. PMID:21159646 doi:10.1158/0008-5472.CAN-10-2101

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