ArticleThe Biochemical journal2014
N-terminus of the protein kinase CLK1 induces SR protein hyperphosphorylation.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Opposing roles of serine and charge in IDR condensate miscibility.Nature chemical biology · 2026Article
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Alternative splicing in pediatric central nervous system tumors highlights oncofetal candidateNeuro-oncology pediatrics · 2026Article
- Characterization of aberrant splicing in pediatric central nervous system tumors revealsbioRxiv : the preprint server for biology · 2025Article
- PROTEIN PHOSPHATASE 2A B'η drives spliceosome subunit dephosphorylation to mediate alternative splicing following heat stress.The Plant cell · 2025Article
- Identification and Biological Evaluation of a Novel CLK4 Inhibitor Targeting Alternative Splicing in Pancreatic Cancer Using Structure-Based Virtual Screening.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The early macrophage response to pathogens requires dynamic regulation of the nuclear paraspeckle.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- An AKT1-and TRIM21-mediated phosphodegron controls proteasomal degradation of HuR enabling cell survival under heat shock.iScience · 2023Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- SPHINX-Based Combination Therapy as a Potential Novel Treatment Strategy for Acute Myeloid Leukaemia.British journal of biomedical science · 2023Article
- Article
- Oncogenic dysregulation of pre-mRNA processing by protein kinases: challenges and therapeutic opportunities.The FEBS journal · 2021Review
- The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins.Journal of molecular biology · 2021Article
- CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer.Journal of hematology & oncology · 2021Article
- 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
- 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
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
SR proteins are essential splicing factors that are regulated through multisite phosphorylation of their RS (arginine/serine-rich) domains by two major families of protein kinases. The SRPKs (SR-specific protein kinases) efficiently phosphorylate the arginine/serine dipeptides in the RS domain using a conserved docking groove in the kinase domain. In contrast, CLKs (Cdc2-like kinases) lack a docking groove and phosphorylate both arginine/serine and serine-proline dipeptides, modifications that generate a hyperphosphorylated state important for unique SR protein-dependent splicing activities. All CLKs contain long flexible N-terminal extensions (140-300 residues) that resemble the RS domains present in their substrate SR proteins. We showed that the N-terminus in CLK1 contacts both the kinase domain and the RS domain of the SR protein SRSF1 (SR protein splicing factor 1). This interaction not only is essential for facilitating hyperphosphorylation, but also induces co-operative binding of SRSF1 to RNA. The N-terminus of CLK1 enhances the total phosphoryl contents of a panel of physiological substrates including SRSF1, SRSF2, SRSF5 and Tra2β1 (transformer 2β1) by 2-3-fold. These findings suggest that CLK1-dependent hyperphosphorylation is the result of a general mechanism in which the N-terminus acts as a bridge connecting the kinase domain and the RS domain of the SR protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.