Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4
Aran, Veronica and Bryant, Nia J and Gould, Gwyn W (2011) Tyrosine phosphorylation of Munc18c on residue 521 abrogates binding to Syntaxin 4. BMC Biochemistry, 12. 19. ISSN 1471-2091 (https://doi.org/10.1186/1471-2091-12-19)
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Abstract
Background: Insulin stimulates exocytosis of GLUT4 from an intracellular store to the cell surface of fat and muscle cells. Fusion of GLUT4-containing vesicles with the plasma membrane requires the SNARE proteins Syntaxin 4, VAMP2 and the regulatory Sec1/Munc18 protein, Munc18c. Syntaxin 4 and Munc18c form a complex that is disrupted upon insulin treatment of adipocytes. Munc18c is tyrosine phosphorylated in response to insulin in these cells. Here, we directly test the hypothesis that tyrosine phosphorylation of Munc18c is responsible for the observed insulin-dependent abrogation of binding between Munc18c and Syntaxin 4. Results: We show that Munc18c is directly phosphorylated by recombinant insulin receptor tyrosine kinase in vitro. Using pull-down assays, we show that phosphorylation abrogates binding of Munc18c to both Syntaxin 4 and the v-SNARE VAMP2, as does the introduction of a phosphomimetic mutation into Munc18c (Y521E). Conclusion: Our data indicate that insulin-stimulated tyrosine phosphorylation of Munc18c impairs the ability of Munc18c to bind its cognate SNARE proteins, and may therefore represent a regulatory step in GLUT4 traffic.
ORCID iDs
Aran, Veronica, Bryant, Nia J and Gould, Gwyn W ORCID: https://orcid.org/0000-0001-6571-2875;-
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Item type: Article ID code: 70243 Dates: DateEvent6 May 2011Published6 May 2011AcceptedSubjects: Science > Microbiology
Medicine > Therapeutics. PharmacologyDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 24 Oct 2019 07:59 Last modified: 12 Sep 2024 00:52 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/70243