| First Author | Sripada A | Year | 2021 |
| Journal | PLoS Biol | Volume | 19 |
| Issue | 3 | Pages | e3001063 |
| PubMed ID | 33684096 | Mgi Jnum | J:305803 |
| Mgi Id | MGI:6515496 | Doi | 10.1371/journal.pbio.3001063 |
| Citation | Sripada A, et al. (2021) Sprouty2 positively regulates T cell function and airway inflammation through regulation of CSK and LCK kinases. PLoS Biol 19(3):e3001063 |
| abstractText | 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. |
