The production of soluble C-type lectin-like receptor 2 is a regulated process.

C-type lectin-like receptor 2 (CLEC-2) is a newly identified type II transmembrane protein belonging to the C-type lectin family molecules, which acts as a cell-surface receptor for snake venom toxin rhodocytin and tumor antigen podoplanin. We previously demonstrated that the full-length mouse CLEC-2 (mCLEC-2) can be cleaved into soluble form. Elevated levels of soluble forms of membrane proteins in circulating blood may reflect increased expression of membrane proteins and disease activities. In the present study, we clarified the domain and sites contributing to the production of soluble mCLEC-2. The shedding process can be positively regulated by protein kinase C (PKC). Moreover, we explored the possibility that human CLEC-2 (hCLEC-2) may also be proteolyticly cleaved and released as a soluble form. We have observed that the production of soluble hCLEC-2 could be induced by phorbol ester (PMA) in cells stably transfected with hCLEC-2 cDNA. Further studies may explore therapeutic and diagnostic applications of soluble hCLEC-2 in platelet-related diseases.