Academic Journal
Lysine Acetylation Reshapes the Downstream Signaling Landscape of Vav1 in Lymphocytes
| العنوان: | Lysine Acetylation Reshapes the Downstream Signaling Landscape of Vav1 in Lymphocytes |
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| المؤلفون: | Rodríguez-Fdez, Sonia, Fernández-Nevado, Lucía, Lorenzo-Martín, L. Francisco, Bustelo, Xosé R. |
| المساهمون: | Junta de Castilla y León, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Asociación Española Contra el Cáncer, Ministerio de Educación, Cultura y Deporte (España) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute |
| سنة النشر: | 2020 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Vav, Guanosine nucleotide exchange factor, Rac1, Rho, JNK, NFAT, T cell receptor, Acetylation, Tyrosine phosphorylation, Adaptor |
| الوصف: | © 2020 by the authors ; Vav1 works both as a catalytic Rho GTPase activator and an adaptor molecule. These functions, which are critical for T cell development and antigenic responses, are tyrosine phosphorylation-dependent. However, it is not known whether other posttranslational modifications can contribute to the regulation of the biological activity of this protein. Here, we show that Vav1 becomes acetylated on lysine residues in a stimulation- and SH2 domain-dependent manner. Using a collection of both acetylation- and deacetylation-mimicking mutants, we show that the acetylation of four lysine residues (Lys222, Lys252, Lys587, and Lys716) leads to the downmodulation of the adaptor function of Vav1 that triggers the stimulation of the nuclear factor of activated T cells (NFAT). These sites belong to two functional subclasses according to mechanistic criteria. We have also unveiled additional acetylation sites potentially involved in either the stimulation (Lys782) or the downmodulation (Lys335, Lys374) of specific Vav1-dependent downstream responses. Collectively, these results indicate that Nε-lysine acetylation can play variegated roles in the regulation of Vav1 signaling. Unlike the case of the tyrosine phosphorylation step, this new regulatory layer is not conserved in other Vav family paralogs. ; X.R.B. is supported by grants from the Castilla-León Government (CLC-2017-01), the Spanish Ministry of Science, Innovation, and Universities (MSIU) (RTI2018-096481-B-I00), and the Spanish Association against Cancer (GC16173472GARC). X.R.B.’s institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Ministry of Education of the Castilla-León Government (CLC-2017-01). S.R.-F. and L.F.L.-M. contracts have been supported by funding from the MISIU (S.R.-F., BES-2013-063573), the Spanish Ministry of Education, Culture, and Sports (L.F.L.-M., FPU13/02923), and the CLC-2017-01 grant (S.R.-F. and L.F.L.-M.). L.F.-N. is supported by the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2073-4409 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096481-B-I00; RTI2018-096481-B-I00/AEI/10.13039/501100011033; Publisher's version; http://dx.doi.org/10.3390/cells9030609; Sí; Cells 9(3): 609 (2020); http://hdl.handle.net/10261/230874; http://dx.doi.org/10.13039/501100011033; http://dx.doi.org/10.13039/501100003176; http://dx.doi.org/10.13039/501100014180 |
| DOI: | 10.3390/cells9030609 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100003176 |
| DOI: | 10.13039/501100014180 |
| الاتاحة: | http://hdl.handle.net/10261/230874 https://doi.org/10.3390/cells9030609 https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100003176 https://doi.org/10.13039/501100014180 |
| Rights: | open |
| رقم الانضمام: | edsbas.9F2F6463 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20734409 |
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| DOI: | 10.3390/cells9030609 |