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Critical role of Lck in L‐selectin signaling induced by sulfatides engagement
Author(s) -
Xu Ting,
Chen Liang,
Shang Xin,
Cui Lingling,
Luo Jixian,
Chen Cuixia,
Ba Xueqing,
Zeng Xianlu
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0208084
Subject(s) - proto oncogene tyrosine protein kinase src , microbiology and biotechnology , phosphorylation , biology , small interfering rna , sh2 domain , gene knockdown , signal transduction , kinase , tyrosine phosphorylation , tyrosine kinase , sh3 domain , rna , cell culture , biochemistry , genetics , gene
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.