ArticleThe Journal of biological chemistry2010
Murine protein serine/threonine kinase 38 stimulates TGF-beta signaling in a kinase-dependent manner via direct phosphorylation of Smad proteins.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Discovery of the MELK-Nucleostemin Axis in Glioblastoma: Implications for p53 Regulation and Tumor Progression.Journal of microbiology and biotechnology · 2026Article
- The role of MELK in cancer: mechanisms and therapeutic options.Frontiers in oncology · 2026Review
- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Targeting MELK in tumor cells and tumor microenvironment: from function and mechanism to therapeutic application.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- LINCRNA01094 Promotes Renal Interstitial Fibrosis via the Mir-513b-5p/ MELK/Smad3 Axis.Endocrine, metabolic & immune disorders drug targets · 2025Article
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Investigating underlying molecular mechanisms, signaling pathways, emerging therapeutic approaches in pancreatic cancer.Frontiers in oncology · 2024Review
- Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- PRMT5 methylating SMAD4 activates TGF-β signaling and promotes colorectal cancer metastasis.Oncogene · 2023Article
- TGF-β Inhibitors for Therapeutic Management of Kidney Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2022Review
- SMAD4, activated by the TCR-triggered MEK/ERK signaling pathway, critically regulates CD8Science advances · 2022Article
- The multifunctional adaptor protein HIP-55 couples Smad7 to accelerate TGF-β type I receptor degradation.Acta pharmacologica Sinica · 2022Article
- TGF-β Signaling.Biomolecules · 2020Review
- Upregulated MELK Leads to Doxorubicin Chemoresistance and M2 Macrophage Polarization via the miR-34a/JAK2/STAT3 Pathway in Uterine Leiomyosarcoma.Frontiers in oncology · 2020Article
- Inhibition of MELK Protooncogene as an Innovative Treatment for Intrahepatic Cholangiocarcinoma.Medicina (Kaunas, Lithuania) · 2019Article
- Thr55 phosphorylation of p21 by MPK38/MELK ameliorates defects in glucose, lipid, and energy metabolism in diet-induced obese mice.Cell death & disease · 2019Article
- Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity.Cell death & disease · 2018Article
- Dual Roles of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) in Redox-Sensitive Signaling Pathways Related to Cancer Development.Oxidative medicine and cellular longevity · 2018Review
- Stent-Jailing Technique Reduces Aneurysm Recurrence More Than Stent-Jack Technique by Causing Less Mechanical Forces and Angiogenesis and Inhibiting TGF-β/Smad2,3,4 Signaling Pathway in Intracranial Aneurysm Patients.Frontiers in physiology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The present study demonstrated that murine protein serine/threonine kinase 38 (MPK38) coimmunoprecipitates with Smad proteins (Smad2, -3, -4, and -7) and that this association is mediated by the catalytic kinase domain of MPK38. The association between MPK38 and Smad2, -3, and -4 was significantly increased by TGF-β or ASK1 signals, whereas these signals decreased association of MPK38 with Smad7. MPK38 stimulated TGF-β-induced transcription required for TGF-β-mediated biological functions, such as apoptosis and cell growth arrest, in a kinase-dependent manner. Knockdown of endogenous MPK38 showed an opposite effect, inhibiting TGF-β signaling. MPK38-mediated phosphorylation of Smad proteins (Ser(245) of Smad2, Ser(204) of Smad3, Ser(343) of Smad4, and Thr(96) of Smad7) was also found to be crucial to the positive regulation of TGF-β signaling induced by MPK38. In addition, MPK38 enhanced nuclear translocation of Smad3, as well as redistribution of Smad7 from the nucleus to the cytoplasm, in response to TGF-β. Together, these results indicate that MPK38 functions as a stimulator of TGF-β signaling through direct interaction with and phosphorylation of Smad proteins.
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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.