Sprouty2 positively regulates T cell function and airway inflammation through regulation of CSK and LCK kinases.
PLoS Biol
; 19(3): e3001063, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33684096
ABSTRACT
The function of Sprouty2 (Spry2) in T cells is unknown. Using 2 different (inducible and T cell-targeted) knockout mouse strains, we found that Spry2 positively regulated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling by modulating the activity of LCK. Spry2-/- CD4+ T cells were unable to activate LCK, proliferate, differentiate into T helper cells, or produce cytokines. Spry2 deficiency abrogated type 2 inflammation and airway hyperreactivity in a murine model of asthma. Spry2 expression was higher in blood and airway CD4+ T cells from patients with asthma, and Spry2 knockdown impaired human T cell proliferation and cytokine production. Spry2 deficiency up-regulated the lipid raft protein caveolin-1, enhanced its interaction with CSK, and increased CSK interaction with LCK, culminating in augmented inhibitory phosphorylation of LCK. Knockdown of CSK or dislodgment of caveolin-1-bound CSK restored ERK1/2 activation in Spry2-/- T cells, suggesting an essential role for Spry2 in LCK activation and T cell function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
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Proteína Tirosina Quinase p56(lck) Linfócito-Específica
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteína Tirosina Quinase CSK
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Proteínas de Membrana
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article