Serine residues in the LAT adaptor are essential for TCR-dependent signal transduction

Journal of Leukocyte Biology

Francisco García-Cózar¹  Pedro Aparicio⁴  Rut Valdor²  Enrique Aguado #¹  Antonio Alonso–⁶  José Yélamos³  Bernard Malissen and⁵  Antonio García-Blesa¹  Mario Martínez-Florensa⁴  Alba Muñoz-Suano¹  Margarita Domínguez-Villar¹ 

[1]  Universidad de CÃdiz and #Fundación para la Gestión de la Investigación Biomédica de CÃdiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Puerto Real, Spain;#Fundación para la Gestión de la Investigación Biomédica de CÃdiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Puerto Real, Spain; Unidad de Transplantes, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain;#Fundación para la Gestión de la Investigación Biomédica de CÃdiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Puerto Real, Spain; Departamento de Inmunología, IMIM-Hospital del Mar, Barcelona, Spain;Departamento de Bioquimíca, Biología Molecular B e Inmunología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain; #Fundación para la Gestión de la Investigación Biomédica de CÃdiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Puerto Real, Spain;;#Fundación para la Gestión de la Investigación Biomédica de CÃdiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Puerto Real, Spain; Centre d²Immunologie de Marseille-Luminy, Université de la Méditerranée, INSERM U63, CNRS UMR60, Marseille, France#Fundación para la Gestión de la Investigación Biomédica de CÃdiz, Hospital Universitario de Puerto Real, Unidad de Investigación, Puerto Real, Spain; –Servicio de Inmunología, Hospital Carlos Haya, Universidad de MÃlaga, Spain;

关键词: CD3;    signaling;    PLC-γ1;    MAPK kinases;   

DOI  :  10.1189/jlb.0509342

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The adaptor protein LAT has a prominent role in the transduction of intracellular signals elicited by the TCR/CD3 complex. Upon TCR engagement, LAT becomes tyrosine-phosphorylated and thereby, recruits to the membrane several proteins implicated in the activation of downstream signaling pathways. However, little is known about the role of other conserved motifs present in the LAT sequence. Here, we report that the adaptor LAT contains several conserved serine-based motifs, which are essential for proper signal transduction through the TCR. Mutation of these serine motifs in the human T cell line Jurkat prevents proper calcium influx, MAPK activation, and IL-2 production in response to TCR/CD3 stimulation. Moreover, this mutant form of LAT has a reduced ability to bind to PLC-γ1 and SLP-76, although phosphorylation of tyrosine residues 132, 171, and 191 is not decreased, raising a possible role for the serine-based motifs of LAT for the binding of important partners. The functional role of LAT serine-based motifs in signal transduction could be mediated by an effect on tyrosine phosphorylation, as their mutation significantly diminishes the phosphorylation of tyrosine residue 226. In addition, these serine motifs seem to have a regulatory role, given that upon their mutation, ZAP-70 shows enhanced phosphorylation. Therefore, the LAT serine-based motifs likely regulate signaling pathways that are essential for T cell physiology.

【 授权许可】

Unknown