Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1

0506029 - ÚMG 2020 RIV CH eng J - Journal Article
Klebanovych, Anastasiya - Sládková, Vladimíra - Sulimenko, Tetyana - Vosecká, Věra - Rubíková, Zuzana - Čapek, Martin - Dráberová, Eduarda - Dráber, Pavel - Sulimenko, Vadym
Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1.
Cells. Roč. 8, č. 4 (2019), č. článku 345. E-ISSN 2073-4409
R&D Projects: GA ČR GA16-25159S; GA ČR GA16-23702S; GA ČR(CZ) GA17-11898S; GA ČR(CZ) GA18-27197S; GA MŠMT(CZ) LM2015062; GA MŠMT LO1419; GA MŠMT(CZ) LTAUSA17052; GA MŠMT(CZ) EF16_013/0001775
Institutional support: RVO:68378050
Keywords : gamma-tubulin complexes * kinase * phosphorylation * syk * fyn * degranulation * centrosome * receptor * cycle * lyn
OECD category: Cell biology
Impact factor: 4.366, year: 2019
Method of publishing: Open access
https://www.mdpi.com/2073-4409/8/4/345

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.
Permanent Link: http://hdl.handle.net/11104/0297515