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Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1
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SYSNO ASEP 0506029 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1 Author(s) Klebanovych, Anastasiya (UMG-J)
Sládková, Vladimíra (UMG-J)
Sulimenko, Tetyana (UMG-J)
Vosecká, Věra (UMG-J)
Rubíková, Zuzana (UMG-J)
Čapek, Martin (UMG-J)
Dráberová, Eduarda (UMG-J) RID, ORCID
Dráber, Pavel (UMG-J) RID, ORCID
Sulimenko, Vadym (UMG-J) RID, ORCIDNumber of authors 9 Article number 345 Source Title Cells. - : MDPI
Roč. 8, č. 4 (2019)Number of pages 23 s. Publication form Print - P Language eng - English Country CH - Switzerland Keywords gamma-tubulin complexes ; kinase ; phosphorylation ; syk ; fyn ; degranulation ; centrosome ; receptor ; cycle ; lyn Subject RIV EB - Genetics ; Molecular Biology OECD category Cell biology R&D Projects GA16-25159S GA ČR - Czech Science Foundation (CSF) GA16-23702S GA ČR - Czech Science Foundation (CSF) GA17-11898S GA ČR - Czech Science Foundation (CSF) GA18-27197S GA ČR - Czech Science Foundation (CSF) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LO1419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LTAUSA17052 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000467304300059 DOI 10.3390/cells8040345 Annotation The antigen-mediated activation of mast cells initiates signaling events leading to their degranulation, to the release of inflammatory mediators, and to the synthesis of cytokines and chemokines. Although rapid and transient microtubule reorganization during activation has been described, the molecular mechanisms that control their rearrangement are largely unknown. Microtubule nucleation is mediated bytubulin complexes. In this study, we report on the regulation of microtubule nucleation in bone marrow-derived mast cells (BMMCs) by Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1, Ptpn6). Reciprocal immunoprecipitation experiments and pull-down assays revealed that SHP-1 is present in complexes containingtubulin complex proteins and protein tyrosine kinase Syk. Microtubule regrowth experiments in cells with deleted SHP-1 showed a stimulation of microtubule nucleation, and phenotypic rescue experiments confirmed that SHP-1 represents a negative regulator of microtubule nucleation in BMMCs. Moreover, the inhibition of the SHP-1 activity by inhibitors TPI-1 and NSC87877 also augmented microtubule nucleation. The regulation was due to changes intubulin accumulation. Further experiments with antigen-activated cells showed that the deletion of SHP-1 stimulated the generation of microtubule protrusions, the activity of Syk kinase, and degranulation. Our data suggest a novel mechanism for the suppression of microtubule formation in the later stages of mast cell activation. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2020 Electronic address https://www.mdpi.com/2073-4409/8/4/345
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