title: Critical role of Lck in L-selectin signaling induced by sulfatides engagement.
abstract: Recruitment of leukocytes onto inflamed tissues is an important physiological event, in which L-selectin plays an essential role in initial leukocyte capture and at the same time, triggers cell signaling. Lck is a member of the Src family of protein tyrosine kinases and is critical for T cell activation triggered by receptor ligation. Here, we demonstrated that Lck was associated directly with and phosphorylated the L-selectin cytoplasmic tail upon L-selectin engagement with sulfatides. Through the direct interaction with ZAP-70 and c-Abl via its Src homology 2 (SH2) and SH3 domains, Lck organized a signaling complex at the cytoplasmic tail of L-selectin. In the cells with Lck knockdown by small interfering RNA treatment, L-selectin signaling was suppressed dramatically, as indicated by reduced phosphorylation of c-Abl and ZAP-70. Re-expression of wild-type or constitutively active but not kinase-dead murine Lck rescued the phosphorylation completely, but the SH2 domain mutant or the SH3/SH2 double mutant of murine Lck had no effect. These results suggest that Lck plays a critical role in L-selectin signaling upon sulfatides stimulation.
authors.affiliation: Northeast Normal University, Changchun, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Shang
authors.forename: Lingling
authors.initials: L
authors.lastname: Cui
authors.forename: Jixian
authors.initials: J
authors.lastname: Luo
authors.forename: Cuixia
authors.initials: C
authors.lastname: Chen
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
mesh_terms: D006801:Humans; D019169:Jurkat Cells; D019041:L-Selectin / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D013433:Sulfoglycosphingolipids; D019041:L-Selectin; D019000:Phosphotyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)