ArticlePloS one2013
Clk/STY (cdc2-like kinase 1) and Akt regulate alternative splicing and adipogenesis in 3T3-L1 pre-adipocytes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Mesoscale proximity labeling at chromatin leads to identification of small molecule mechanism of action.Nature communications · 2026Article
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- Decoding SR protein regulation: kinases, phosphatases, and therapeutic targeting strategies.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Induction of beige-like adipocyte markers and functions in 3T3-L1 cells by Clk1 and PKCβII inhibitory molecules.Journal of cellular and molecular medicine · 2022Article
- Oncogenic dysregulation of pre-mRNA processing by protein kinases: challenges and therapeutic opportunities.The FEBS journal · 2021Review
- CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer.Scientific reports · 2021Article
- Regulatory roles and mechanisms of alternative RNA splicing in adipogenesis and human metabolic health.Cell & bioscience · 2021Review
- Inhibition of a Novel CLK1-THRAP3-PPARγ Axis Improves Insulin Sensitivity.Frontiers in physiology · 2021Article
- Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- Availability of splicing factors in the nucleoplasm can regulate the release of mRNA from the gene after transcription.PLoS genetics · 2019Article
- Relationship between lipid droplets size and integrated optical density.European journal of histochemistry : EJH · 2019Article
- Analysis of long noncoding RNA and mRNA using RNA sequencing during the differentiation of intramuscular preadipocytes in chicken.PloS one · 2017Article
- The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages.Scientific reports · 2016Article
- CDK13, a Kinase Involved in Pre-mRNA Splicing, Is a Component of the Perinucleolar Compartment.PloS one · 2016Article
- Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment.Molecules (Basel, Switzerland) · 2015Article
- Impacts of Alternative Splicing Events on the Differentiation of Adipocytes.International journal of molecular sciences · 2015Review
- Article
- The adipogenic transcriptional cofactor ZNF638 interacts with splicing regulators and influences alternative splicing.Journal of lipid research · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The development of adipocytes from their progenitor cells requires the action of growth factors signaling to transcription factors to induce the expression of adipogenic proteins leading to the accumulation of lipid droplets, induction of glucose transport, and secretion of adipokines signaling metabolic events throughout the body. Murine 3T3-L1 pre-adipocytes sequentially express all the proteins necessary to become mature adipocytes throughout an 8-10 day process initiated by a cocktail of hormones. We examined the role of Clk/STY or Clk1, a cdc2-like kinase, in adipogenesis since it is known to be regulated by Akt, a pivotal kinase in development. Inhibition of Clk1 by a specific inhibitor, TG003, blocked alternative splicing of PKCβII and expression of PPARγ1 and PPARγ2. SiRNA depletion of Clk1 resulted in early expression of PKCβII and sustained PKCβI expression. Since Clk1 is a preferred Akt substrate, required for phosphorylation of splicing factors, mutation of Clk1 Akt phosphorylation sites was undertaken. Akt sites on Clk1 are in the serine/arginine-rich domain and not the kinase domain. Mutation of single and multiple sites resulted in dysregulation of PKCβII, PKCβI, and PPARγ1&2 expression. Additionally, adipogenesis was blocked as assessed by Oil Red O staining, adiponectin, and Glut1 and 4 expression. Immunofluorescence microscopy revealed that Clk1 triple mutant cDNA, transfected into pre-adipocytes, resulted in excluding SRp40 (SFSR6) from co-localizing to the nucleus with PFS, a perispeckle specific protein. This study demonstrates the role of Akt and Clk1 kinases in the early differentiation of 3T3-L1 cells to adipocytes.
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Registered trials
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