ArticleThe Biochemical journal2015
Nuclear protein kinase CLK1 uses a non-traditional docking mechanism to select physiological substrates.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Interplay Between CMGC Kinases Targeting SR Proteins and Viral Replication: Splicing and Beyond.Frontiers in microbiology · 2021Review
- Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential.International journal of molecular sciences · 2020Review
- LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation.The EMBO journal · 2020Article
- Redox-dependent gating of VDAC by mitoNEET.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Disordered protein interactions for an ordered cellular transition: Cdc2-like kinase 1 is transported to the nucleus via its Ser-Arg protein substrate.The Journal of biological chemistry · 2019Article
- Hypoxia leads to significant changes in alternative splicing and elevated expression of CLK splice factor kinases in PC3 prostate cancer cells.BMC cancer · 2018Article
- Mobilization of a splicing factor through a nuclear kinase-kinase complex.The Biochemical journal · 2018Article
- Redirecting SR Protein Nuclear Trafficking through an Allosteric Platform.Journal of molecular biology · 2017Article
- Release of SR Proteins from CLK1 by SRPK1: A Symbiotic Kinase System for Phosphorylation Control of Pre-mRNA Splicing.Molecular cell · 2016Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Phosphorylation-dependent cell communication requires enzymes that specifically recognize key proteins in a sea of similar, competing substrates. The protein kinases achieve this goal by utilizing docking grooves in the kinase domain or heterologous protein adaptors to reduce 'off pathway' targeting. We now provide evidence that the nuclear protein kinase CLK1 (cell division cycle2-like kinase 1) important for splicing regulation departs from these classic paradigms by using a novel self-association mechanism. The disordered N-terminus of CLK1 induces oligomerization, a necessary event for targeting its physiological substrates the SR protein (splicing factor containing a C-terminal RS domain) family of splicing factors. Increasing the CLK1 concentration enhances phosphorylation of the splicing regulator SRSF1 (SR protein splicing factor 1) compared with the general substrate myelin basic protein (MBP). In contrast, removal of the N-terminus or dilution of CLK1 induces monomer formation and reverses this specificity. CLK1 self-association also occurs in the nucleus, is induced by the N-terminus and is important for localization of the kinase in sub-nuclear compartments known as speckles. These findings present a new picture of substrate recognition for a protein kinase in which an intrinsically disordered domain is used to capture physiological targets with similar disordered domains in a large oligomeric complex while discriminating against non-physiological targets.
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