期刊
JOURNAL OF BIOCHEMISTRY
卷 150, 期 2, 页码 127-132出版社
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvr079
关键词
CLEC-2; lymphangiogenesis; platelets; podoplanin; tumour metastasis
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labor and Welfare of Japan
- The Japan Society for the Promotion of Science (JSPS)
- Council for Science and Technology Policy (CSTP)
We have recently identified C-type lectin-like receptor 2 (CLEC-2) as a receptor for the platelet activating snake venom rhodocytin. CLEC-2 elicits powerful platelet activation signals in conjunction with single YxxL motif in its cytoplasmic tail, Src, Syk kinases, and phospholipase C gamma 2. An endogenous ligand of CLEC-2 has been identified as podoplanin, which is a membrane protein of tumour cells and facilitates tumour metastasis by inducing platelet activation. Studies of CLEC-2-deficient mice have revealed several physiological roles of CLEC-2. Podoplanin is also expressed in lymphatic endothelial cells. In the developmental stages, when the primary lymph sac is derived from the cardinal vein, podoplanin activates platelets in lymphatic endothelial cells, which facilitates blood/lymphatic vessel separation. Moreover, CLEC-2 is involved in thrombus stabilization under flow conditions in part through homophilic interactions. The absence of CLEC-2 does not significantly increase bleeding tendency, implying that CLEC-2 may be a good target protein for anti-platelet drugs in addition to anti-metastatic drugs.
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