| Structural highlights
Function
CLK1_HUMAN Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.[1] [2]
Publication Abstract from PubMed
Homeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remain elusive. Furthermore, a thermo-sensor capable of sensing the small temperature differentials leading to temperature-dependent sex determination (TSD) in poikilothermic reptiles has not been identified. Here, we show that the activity of CDC-like kinases (CLKs) is highly responsive to physiological temperature changes, which is conferred by structural rearrangements within the kinase activation segment. Lower body temperature activates CLKs resulting in strongly increased phosphorylation of SR proteins in vitro and in vivo. This globally controls temperature-dependent alternative splicing and gene expression, with wide implications in circadian, tissue-specific, and disease-associated settings. This temperature sensor is conserved across evolution and adapted to growth temperatures of diverse poikilotherms. The dynamic temperature range of reptilian CLK homologs suggests a role in TSD.
A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression.,Haltenhof T, Kotte A, De Bortoli F, Schiefer S, Meinke S, Emmerichs AK, Petermann KK, Timmermann B, Imhof P, Franz A, Loll B, Wahl MC, Preussner M, Heyd F Mol Cell. 2020 Feb 7. pii: S1097-2765(20)30049-6. doi:, 10.1016/j.molcel.2020.01.028. PMID:32059760[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moeslein FM, Myers MP, Landreth GE. The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. J Biol Chem. 1999 Sep 17;274(38):26697-704. PMID:10480872
- ↑ Eisenreich A, Bogdanov VY, Zakrzewicz A, Pries A, Antoniak S, Poller W, Schultheiss HP, Rauch U. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ Res. 2009 Mar 13;104(5):589-99. doi: 10.1161/CIRCRESAHA.108.183905. Epub, 2009 Jan 22. PMID:19168442 doi:10.1161/CIRCRESAHA.108.183905
- ↑ Haltenhof T, Kotte A, De Bortoli F, Schiefer S, Meinke S, Emmerichs AK, Petermann KK, Timmermann B, Imhof P, Franz A, Loll B, Wahl MC, Preussner M, Heyd F. A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression. Mol Cell. 2020 Feb 7. pii: S1097-2765(20)30049-6. doi:, 10.1016/j.molcel.2020.01.028. PMID:32059760 doi:http://dx.doi.org/10.1016/j.molcel.2020.01.028
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