title: Essential in vivo roles of the platelet activation receptor CLEC-2 in tumour metastasis, lymphangiogenesis and thrombus formation.
abstract: 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 Cγ2. 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.
authors.affiliation: Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. katsuei@yamanashi.ac.jp
authors.forename: Katsue
authors.initials: K
authors.lastname: Suzuki-Inoue
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D042583:Lymphangiogenesis / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology*; D015398:Signal Transduction; D013927:Thrombosis / Q000378:metabolism; D014757:Viper Venoms / Q000737:chemistry; D000098853:Podoplanin
chemical_list: D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D014757:Viper Venoms; C104778:CLEC2B protein, human; C490441:Pdpn protein, mouse; D000098853:Podoplanin