Aurora A drives early signalling and vesicle dynamics during T-cell activation

Autor: Noa B. Martín-Cófreces, Ignacio Pérez de Castro, Emilio Camafeita, Francisco Sánchez-Madrid, Balbino Alarcón, Jesús Vázquez, Aldo Borroto, Inmaculada Jorge, Eugenio Bustos-Morán, Guillermo de Cárcer, Marcos Malumbres, Noelia Blas-Rus
Přispěvatelé: Fundación Pro CNIC, Ministerio de Ciencia e Innovación (España), Centro Nacional de Investigaciones Cardiovasculares (España), Instituto de Salud Carlos III, Comunidad de Madrid, Ministerio de Economía y Competitividad (España), UAM. Departamento de Medicina, Centro de Biología Molecular Severo Ochoa (CBM), European Commission, Fundación ProCNIC, European Research Council
Rok vydání: 2016
Předmět:
Antigens
Differentiation
T-Lymphocyte
Male
0301 basic medicine
CD3 Complex
Immunological Synapses
IMMUNOLOGICAL SYNAPSE
T-Lymphocytes
General Physics and Astronomy
TYROSINE KINASE
Lymphocyte Activation
Microtubules
Immunological synapse
Mice
Phosphorylation
IN-VIVO
Aurora Kinase A
A KINASE
Multidisciplinary
hemic and immune systems
Azepines
IMMUNE SYNAPSE
Autophosphorylation
LCK
3. Good health
Cell biology
embryonic structures
Female
biological phenomena
cell phenomena
and immunity
Signal transduction
CENTROSOME MATURATION
Tyrosine kinase
Signal Transduction
Medicina
TIRF MICROSCOPY
Science
Receptors
Antigen
T-Cell
Aurora A kinase
Aurora inhibitor
Mice
Transgenic
chemical and pharmacologic phenomena
macromolecular substances
Biology
Article
General Biochemistry
Genetics and Molecular Biology
ACTIN
03 medical and health sciences
Antigens
CD
Animals
Humans
Immunoprecipitation
Lectins
C-Type
Protein Kinase Inhibitors
CD4+ T lymphocyte
Cytoplasmic Vesicles
T-cell receptor
Interleukin-2 Receptor alpha Subunit
General Chemistry
enzymes and coenzymes (carbohydrates)
Pyrimidines
030104 developmental biology
Gene Expression Regulation
Human cell
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Interleukin-2
ANTIGEN RECEPTOR
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Biblos-e Archivo. Repositorio Institucional de la UAM
Nature Communications, Vol 7, Iss 1, Pp 1-16 (2016)
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Repisalud
Instituto de Salud Carlos III (ISCIII)
Nature Communications
ISSN: 2041-1723
Popis: Aurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3¿-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal.
Spanish Ministry of Economy and Competitiveness, NDISNET-S2011/BMD-2332 from the Comunidad de Madrid ERC-2011-AdG 294340-GENTRIS and ERC-2013-AdG 334763-NOVARIPP. Red Cardiovascular RD 12-0042-0056 from Instituto Salud Carlos III (ISCIII). The Centro Nacional de Investigaciones Cardiovasculares (CNIC, Spain) is supported by the Spanish Ministry of Science and Innovation, and the Pro-CNIC Foundation
Databáze: OpenAIRE
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