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Type of PaperY192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection.
- Source :
-
International Journal of Molecular Sciences . Jul2022, Vol. 23 Issue 13, p7271-N.PAG. 15p. - Publication Year :
- 2022
-
Abstract
- Signaling via the TCR, which is initiated by the Src-family tyrosine kinase Lck, is crucial for the determination of cell fates in the thymus. Because of its pivotal role, ablation of Lck results in a profound block of T-cell development. Here, we show that, in addition to its well-known function in the initiation of TCR signaling, Lck also acts at a more downstream level. This novel function of Lck is determined by the tyrosine residue (Y192) located in its SH2 domain. Thymocytes from knock-in mice expressing a phosphomimetic Y192E mutant of Lck initiate TCR signaling upon CD3 cross-linking up to the level of PLC-γ1 phosphorylation. However, the activation of downstream pathways including Ca2+ influx and phosphorylation of Erk1/2 are impaired. Accordingly, positive and negative selections are blocked in LckY192E knock-in mice. Collectively, our data indicate that Lck has a novel function downstream of PLCγ-1 in the regulation of thymocyte differentiation and selection. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CELL determination
*PROTEIN-tyrosine kinases
*THYMOCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 23
- Issue :
- 13
- Database :
- Academic Search Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 157995692
- Full Text :
- https://doi.org/10.3390/ijms23137271