TCR activation stimulates regulated intramembrane proteolysis of L-selectin by presenilin 1 and localized proteasomal degradation of the cytoplasmic tail.

ABSTRACT: Leucocyte (L)-selectin is essential for mounting protective immunity to pathogens. As well as regulating leucocyte recruitment, it also regulates their activation and differentiation inside tissues thereby shaping local immune responses. The biochemical signals that regulate these diverse functions of L-selectin are poorly understood. Leucocyte activation induces proteolytic shedding of L-selectin ectodomain (ECD) but the impact of ECD shedding on signaling downstream of L-selectin is not known. In T cells, there is substantial overlap between signaling downstream of L-selectin and the T-cell receptor (TCR). Cross-linking of L-selectin stimulates phosphorylation of the cytoplasmic tail and forward signaling via the nonreceptor tyrosine kinases Lck and Zap70. Cross-linking of TCR induces ph

SUBMITTER: Moon OR 

PROVIDER: S-EPMC12355078 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature