Platelet activating receptor CLEC-2 has been identified on platelet surface a decade ago. The only confirmed endogenous CLEC-2 agonist is podoplanin. Podoplanin is a transmembrane protein expressed by lymphatic endothelial cells, reticular fibroblastic cells in lymph nodes, kidney podocytes and by cells of certain tumors. CLEC-2 and podoplanin are involved in the processes of embryonic development (blood-lymph vessel separation and angiogenesis), maintaining of vascular integrity of small vessels during inflammation and prevention of blood-lymphatic mixing in high endothelial venules. However, CLEC-2 and podoplanin are contributing to tumor methastasis progression, Salmonella sepsis, deep-vein thrombosis. CLEC-2 signalling cascade includes tyrosine-kinases (Syk, SFK, Btk) as well as adapter LAT and phospholipase Cg2, which induces calcium signalling. CLEC-2, podoplanin and proteins, participating in CLEC-2 signalling cascade, are perspective targets for antithrombotic therapy.
Aktiviruiushchiĭ retseptor semeĭstva lektinovykh tipa S (C-type lectin, CLEC), CLEC-2, byl obnaruzhen na trombotsitakh cheloveka okolo desiati let nazad. Izvestnym éndogennym ligandom CLEC-2 iavliaetsia membrannyĭ belok podoplanin, éksponiruemyĭ kletkami limfaticheskogo éndoteliia, retikuliarnymi fibroblastami v limfaticheskikh uzlakh, podotsitami pochek, a takzhe kletkami nekotorykh opukholeĭ. CLEC-2 i podoplanin uchastvuiut v metastazirovanii, sepsise, razvitii trombozov glubokikh ven. Signal'nyĭ kaskad CLEC-2 vkliuchaet v sebia riad tirozinkinaz (Syk, SFK, Btk), a takzhe adapter LAT i fosfolipazu Cg2, kotoraia zapuskaet kal'tsievuiu signalizatsiiu. CLEC-2 i podoplanin, a takzhe uchastniki signal'nogo kaskada CLEC-2, rassmatrivaiutsia kak misheni dlia antitrombotsitarnoĭ terapii.
Keywords: CLEC-2 receptor; lymphangiogenesis; methastasis; platelet; podoplanin; tyrosine kinases.