A NOVEL REGULATORY MECHANISM OF A HUMAN LYMPHOCYTE METALLOPROTEASE

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ADAMs (a disintegrin and metalloprotease) are multidomain proteins that participate in a wide array of biological events such as fertilization, neurogenesis, and immune response as well as disease states such as tumor onset/progression, chronic inflammation, and Alzheimer's. The two defining domain structures, a disintegrin and metalloprotease, have established ADAMs as a novel class of proteins possessing both adhesive and proteolytic properties. Thirty-three ADAMs have been identified in various mammalian species with only one third possessing a consensus site indicative of a functional metalloprotease. Even though the majority of identified ADAM members lack proteolytic activity, the biological role of these inactive ADAMs is poorly defined. Active ADAM metalloproteases are well-characterized ectodomain sheddases capable of regulating extracelluar signals by obligate processing/cleavage of bioactive factors (e.g. cytokines and growth factors) from the cell surface. Both active and inactive ADAM members are capable of mediating integrin-dependent cell adhesion through their disintegrin domains. The interdependence of the proteolytic and adhesive specificities remains largely undefined. Based upon current models that nonproteolytic ADAM domains govern protease specificity, this proposal aims to delineate the role of inactive ADAMs in influencing ADAM-mediated shedding.