ArticleThe Journal of biological chemistry2007
WNK1 is a novel regulator of Munc18c-syntaxin 4 complex formation in soluble NSF attachment protein receptor (SNARE)-mediated vesicle exocytosis.
Article in The Journal of biological chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling.bioRxiv : the preprint server for biology · 2025Article
- WNK1-dependent water influx is required for CD4Nature communications · 2025Article
- WNK1 is required during male pachynema to sustain fertility.iScience · 2023Article
- B cell-intrinsic requirement for WNK1 kinase in antibody responses in mice.The Journal of experimental medicine · 2023Article
- WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle.FEBS open bio · 2018Article
- WNK1 kinase and its partners Akt, SGK1 and NBC-family NaOncotarget · 2018Article
- Disruption of protein complexes containing protein phosphatase 2B and Munc18c reduces the secretion of von Willebrand factor from endothelial cells.Journal of thrombosis and haemostasis : JTH · 2017Article
- Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Identification of the WNK-SPAK/OSR1 signaling pathway in rodent and human lenses.Investigative ophthalmology & visual science · 2014Article
- Doc2b serves as a scaffolding platform for concurrent binding of multiple Munc18 isoforms in pancreatic islet β-cells.The Biochemical journal · 2014Article
- WNK1 is required for mitosis and abscission.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- The WNKs: atypical protein kinases with pleiotropic actions.Physiological reviews · 2011Review
- Protein kinase WNK1 promotes cell surface expression of glucose transporter GLUT1 by regulating a Tre-2/USP6-BUB2-Cdc16 domain family member 4 (TBC1D4)-Rab8A complex.The Journal of biological chemistry · 2010Article
- Emerging roles for WNK kinases in cancer.Cellular and molecular life sciences : CMLS · 2010Review
- Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4.American journal of physiology. Regulatory, integrative and comparative physiology · 2010Review
- WNK kinases and blood pressure control.Current hypertension reports · 2009Review
- Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.Molecular psychiatry · 2009Article
- In vivo phosphoproteome of human skeletal muscle revealed by phosphopeptide enrichment and HPLC-ESI-MS/MS.Journal of proteome research · 2009Article
- Cab45b, a Munc18b-interacting partner, regulates exocytosis in pancreatic beta-cells.The Journal of biological chemistry · 2009Article
- Mechanisms of biphasic insulin-granule exocytosis - roles of the cytoskeleton, small GTPases and SNARE proteins.Journal of cell science · 2009Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Defects in soluble NSF attachment protein receptor (SNARE)-mediated granule exocytosis occur in islet beta cells, adipocytes, and/or skeletal muscle cells correlate with increased susceptibility to insulin resistance and diabetes. The serine/threonine kinase WNK1 (with no K (lysine)) has recently been implicated in exocytosis and is expressed in all three of these cell types. To search for WNK1 substrates related to exocytosis, we conducted a WNK1 two-hybrid screen, which yielded Munc18c. Munc18c is known to be a key regulator of accessibility of the target membrane (t-SNARE) protein syntaxin 4 to participate in SNARE core complex assembly, although a paucity of Munc18c-binding factors has precluded discovery of its precise functions. To validate WNK1 as a new Munc18c-interacting partner, the direct interaction between WNK1 and Munc18c was confirmed using in vitro binding analysis, and endogenous WNK1-Munc18c complexes were detected in the cytosolic and plasma membrane compartments of the islet beta cell line MIN6. This binding interaction is mediated through the N-terminal 172 residues of Munc18c and the kinase domain residues of WNK1 (residues 159-491). Expression of either of these two minimal interaction domains resulted in inhibition of glucose-stimulated insulin secretion, consistent with a functional importance for the endogenous WNK1-Munc18c complex in exocytosis. Interestingly, Munc18c failed to serve as a WNK1 substrate in kinase activity assays, suggesting that WNK1 functions in SNARE complex assembly outside its role as a kinase. Taken together, these data support a novel role for WNK1 and a new mechanism for the regulation of SNARE complex assembly by WNK1-Munc18c complexes.
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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 Socratic graph.