ArticleThe Journal of biological chemistry2014
LMTK2-mediated phosphorylation regulates CFTR endocytosis in human airway epithelial cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- LMTK2 Inhibits Metastasis of Colon Cancer Cells Through p38 MAPK.Cancer science · 2026Article
- Regulation of CFTR stability at the plasma membrane-Mechanisms and therapeutic opportunities in cystic fibrosis.FEBS letters · 2026Review
- Defining the Active Conformation of Typical Protein Kinase Domains from Substrate-Bound PDB Structures Enables Active-State AlphaFold2 Models for All 437 Human Catalytic Protein Kinases.bioRxiv : the preprint server for biology · 2026Article
- Novel involvement of LMTK2 and EML6 in rheumatoid arthritis: potential biomarkers for disease activity and seronegative patients.Frontiers in immunology · 2026Article
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- LMTK2 switches on canonical TGF-β1 signaling in human bronchial epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- A revised nomenclature for the lemur family of protein kinases.Communications biology · 2024Review
- Molecular mechanisms of cystic fibrosis - how mutations lead to misfunction and guide therapy.Bioscience reports · 2022Review
- Article
- Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021Review
- The multifaceted role of lemur tyrosine kinase 3 in health and disease.Open biology · 2021Review
- Human Bronchial Epithelial Cell Growth on Homologous Versus Heterologous Tissue Extracellular Matrix.The Journal of surgical research · 2021Article
- LMTK2 regulates inflammation in lipopolysaccharide-stimulated BV2 cells.Experimental and therapeutic medicine · 2021Article
- Differential Gene Expression Analysis Reveals Global LMTK2 Regulatory Network and Its Role in TGF-β1 Signaling.Frontiers in oncology · 2021Article
- TGF-β1 Augments the Apical Membrane Abundance of Lemur Tyrosine Kinase 2 to Inhibit CFTR-Mediated Chloride Transport in Human Bronchial Epithelia.Frontiers in cell and developmental biology · 2020Article
- Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer's disease and neocortical Lewy body disease.Scientific reports · 2019Article
- CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathway degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Transforming Growth Factor-β1 Selectively Recruits microRNAs to the RNA-Induced Silencing Complex and Degrades CFTR mRNA under Permissive Conditions in Human Bronchial Epithelial Cells.International journal of molecular sciences · 2019Article
- Unraveling the Function of Lemur Tyrosine Kinase 2 Network.Frontiers in pharmacology · 2019Review
- Network Biology Identifies Novel Regulators of CFTR Trafficking and Membrane Stability.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-)-selective ion channel expressed in fluid-transporting epithelia. Lemur tyrosine kinase 2 (LMTK2) is a transmembrane protein with serine and threonine but not tyrosine kinase activity. Previous work identified CFTR as an in vitro substrate of LMTK2, suggesting a functional link. Here we demonstrate that LMTK2 co-immunoprecipitates with CFTR and phosphorylates CFTR-Ser(737) in human airway epithelial cells. LMTK2 knockdown or expression of inactive LMTK2 kinase domain increases cell surface density of CFTR by attenuating its endocytosis in human airway epithelial cells. Moreover, LMTK2 knockdown increases Cl(-) secretion mediated by the wild-type and rescued ΔF508-CFTR. Compared with the wild-type CFTR, the phosphorylation-deficient mutant CFTR-S737A shows increased cell surface density and decreased endocytosis. These results demonstrate a novel mechanism of the phospho-dependent inhibitory effect of CFTR-Ser(737) mediated by LMTK2 via endocytosis and inhibition of the cell surface density of CFTR Cl(-) channels. These data indicate that targeting LMTK2 may increase the cell surface density of CFTR Cl(-) channels and improve stability of pharmacologically rescued ΔF508-CFTR in patients with cystic fibrosis.
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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.