CLONING OF RAT VITAMIN-K-DEPENDENT GAMMA-GLUTAMYL CARBOXYLASE AND DEVELOPMENTALLY-REGULATED GENE-EXPRESSION IN POSTIMPLANTATION EMBRYOS

Vitamin K-dependent carboxylase catalyzes the posttranslational modifi cation of glutamate to gamma-carboxy-glutamate (Gla) in its substrates , the vitamin K-dependent proteins (VKDPs). This modification is requi red for the activities of the VKDPs. Recent evidence demonstrates prev iously unrecognized roles for VKDPs as signaling molecules important i n the regulation of cell growth, adhesion, and apoptosis, suggesting d evelopmental functions for VKDPs and hence the carboxylase. The tissue distribution and functions of carboxylase in development are unknown. In this study, we isolated and characterized the full-length cDNA enc oding the rat carboxylase and analyzed, at the cellular level, the exp ression of this gene in rat embryos by in situ hybridization. We demon strate that the expression of this gene is highly regulated in a devel opmental and tissue-specific manner. Hepatocytes, the major site of sy nthesis of VKDPs of blood coagulation, express carboxylase mRNA late i n gestation, in contrast to the central nervous system, mesenchymal, a nd skeletal tissues which express carboxylase mRNA early during rat em bryogenesis. The tissue-specific temporal expression of the carboxylas e gene during embryogenesis indicates that vitamin K-dependent carboxy lation and the formation of Gla is developmentally regulated. These st udies suggest that vitamin K-dependent carboxylation is an important m odulator of embryonic VKDP function. (C) 1998 Academic Press.