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Critical Reviews™ in Immunology
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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2019030480
pages 59-81

TAOK3, a Regulator of LCK–SHP-1 Crosstalk during TCR Signaling

João V. S. Ormonde
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; Microbiome and Disease Tolerance Centre, and Department of Microbiology and Immunology, McGill University, Montréal, Quebec
Yan Nie
Department of Biochemistry, McGill University, Montréal, Quebec
Joaquin Madrenas
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; Microbiome and Disease Tolerance Centre, and Department of Microbiology and Immunology, McGill University, Montréal, Quebec

ABSTRACT

Signaling from the T cell receptor for antigen turns on the physiological response of a T cell. The canonical TCR signaling pathway relies on early activation of the Src kinase LCK. This step initiates a cascade of events that lead not only to the phenotypic changes that characterize effector T cells but also to the activation of negative regulatory mechanisms that stop early TCR signaling. These mechanisms ensure qualitative and quantitative fine-tuning of T cell activation. The tyrosine phosphatase SHP-1 is a key player in the downregulation of LCK activation. In this review, we focus on the crosstalk between LCK and SHP-1 and, based on recent data, we introduce the putative kinase TAOK3 as an important regulator of this crosstalk. Given the widespread expression of TAOK3 and SHP-1, we propose that the function of TAOK3 extends beyond T cells and may be fundamental in the regulation of early signaling from receptors that utilize Src kinases.

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