ADAMTS-1 PROTEIN ANCHORS AT THE EXTRACELLULAR-MATRIX THROUGH THE THROMBOSPONDIN TYPE-I MOTIFS AND ITS SPACING REGION

Cellular disintegrin and metalloproteinases (ADAMs) are a family of ge nes with a sequence similar to those of snake venom metalloproteinases and disintegrins. The ADAMTS-1 gene encodes a new type of ADAM protei n with respect to possessing the thrombospondin (TSP) type I motifs. E xpression of the gene is induced in kidney and heart by in vivo admini stration of lipopolysaccharide, suggesting a possible role in the infl ammatory reaction. In this study, we characterized the ADAMTS-1 gene p roduct by using a transient expression system in COS-7 cells. We found that the precursor and processed forms of ADAMTS-1 were secreted from cells. Under normal growth conditions, little or none of both forms w as detected in the cell culture medium, and instead the majority was f ound associated with the extracellular matrix (ECM). In addition, when cells were cultured in the presence of heparin, the mature form of AD AMTS-1 protein was detected in the cell culture medium, suggesting tha t binding of ADAMTS-1 to the ECM is mediated through sulfated glycosam inoglycans such as heparan sulfate. Analyses of deletion mutants of th e ADAMTS-1 protein revealed that the spacer region as well as three TS P type I motifs in the carboxyl-terminal region of the ADAMTS-1 protei n are important for a tight interaction with the ECM. These results su ggest that the ADAMTS-1 is a unique ADAM family protein that anchors a t the ECM.