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Transmembrane Adaptor Protein PAG/CBP Is Involved in both Positive and Negative Regulation of Mast Cell Signaling
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SYSNO ASEP 0440747 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Transmembrane Adaptor Protein PAG/CBP Is Involved in both Positive and Negative Regulation of Mast Cell Signaling Author(s) Dráberová, Lubica (UMG-J) RID
Bugajev, Viktor (UMG-J) RID
Potůčková, Lucie (UMG-J)
Hálová, Ivana (UMG-J) RID, ORCID
Bambousková, Monika (UMG-J)
Polakovičová, Iva (UMG-J)
Xavier, R.J. (US)
Seed, B. (US)
Dráber, Petr (UMG-J) RIDSource Title Molecular and Cellular Biology. - : American Society for Microbiology - ISSN 0270-7306
Roč. 34, č. 23 (2014), s. 4285-4300Number of pages 16 s. Language eng - English Country US - United States Keywords plasma membrane ; cel signaling ; IgE receptor Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA301/09/1826 GA ČR - Czech Science Foundation (CSF) GAP302/10/1759 GA ČR - Czech Science Foundation (CSF) GBP302/12/G101 GA ČR - Czech Science Foundation (CSF) GD204/09/H084 GA ČR - Czech Science Foundation (CSF) LD12073 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA14-00703S GA ČR - Czech Science Foundation (CSF) GA14-09807S GA ČR - Czech Science Foundation (CSF) Institutional support UMG-J - RVO:68378050 UT WOS 000344631500006 DOI 10.1128/MCB.00983-14 Annotation The transmembrane adaptor protein PAG/CBP (here, PAG) is expressed in multiple cell types. Tyrosine-phosphorylated PAG serves as an anchor for C-terminal SRC kinase, an inhibitor of SRC-family kinases. The role of PAG as a negative regulator of immunoreceptor signaling has been examined in several model systems, but no functions in vivo have been determined. Here, we examined the activation of bone marrow-derived mast cells (BMMCs) with PAG knockout and PAG knockdown and the corresponding controls. Our data show that PAG-deficient BMMCs exhibit impaired antigen-induced degranulation, extracellular calcium uptake, tyrosine phosphorylation of several key signaling proteins (including the high-affinity IgE receptor subunits, spleen tyrosine kinase, and phospholipase C), production of several cytokines and chemokines, and chemotaxis. The enzymatic activities of the LYN and FYN kinases were increased in nonactivated cells, suggesting the involvement of a LYN- and/or a FYN-dependent negative regulatory loop. When BMMCs from PAG-knockout mice were activated via the KIT receptor, enhanced degranulation and tyrosine phosphorylation of the receptor were observed. In vivo experiments showed that PAG is a positive regulator of passive systemic anaphylaxis. The combined data indicate that PAG can function as both a positive and a negative regulator of mast cell signaling, depending upon the signaling pathway involved. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2015
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