TAOK3 Regulates Canonical TCR Signaling by Preventing Early SHP-1-Mediated Inactivation of LCK.
J Immunol
; 201(11): 3431-3442, 2018 12 01.
Article
em En
| MEDLINE
| ID: mdl-30373850
ABSTRACT
Activation of LCK is required for canonical TCR signaling leading to T cell responses. LCK activation also initiates a negative feedback loop mediated by the phosphatase SHP-1 that turns off TCR signaling. In this article, we report that the thousand-and-one amino acid kinase 3 (TAOK3) is a key regulator of this feedback. TAOK3 is a serine/threonine kinase expressed in many different cell types including T cells. TAOK3-deficient human T cells had impaired LCK-dependent TCR signaling resulting in a defect in IL-2 response to canonical TCR signaling but not to bacterial superantigens, which use an LCK-independent pathway. This impairment was associated with enhanced interaction of LCK with SHP-1 after TCR engagement and rapid termination of TCR signals, a defect corrected by TAOK3 reconstitution. Thus, TAOK3 is a positive regulator of TCR signaling by preventing premature SHP-1-mediated inactivation of LCK. This mechanism may also regulate signaling by other Src family kinase-dependent receptors.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Proteínas Serina-Treonina Quinases
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Proteína Tirosina Quinase p56(lck) Linfócito-Específica
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Proteína Tirosina Fosfatase não Receptora Tipo 6
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article