The overall goal of this research proposal is to determine the functions and the mechanism of action of three novel amine oxidases, LOXL, LOXL2 and LOXL3 that are structurally and functionally related to lysyl oxidase (LOX). LOX is a copper-dependent amine oxidase that has been known for many years to be responsible for the catalysis of lysine-derived cross-links in the extracellular matrix proteins, elastin and collagen. Alterations in the synthesis and activity of LOX are known to be associated with a variety of acquired and heritable diseases, including skin disorders such as cuffs laxa, Wilson's and Menkes disease. In an attempt to determine the precise role of LOX in such diverse pathologies, these investigators have recently shown that LOX is not just a single enzyme but rather a family of at least four functionally- related but genetically-distinct lysyl oxidases. From preliminary data presented in this application, it is clear that these lysyl oxidases (referred to as lysyl oxidase-like or LOXL proteins) are found in different tissues in both extracellular and intracellular locations. This new family of enzymes therefore has related but distinct functions in different tissues and the work proposed in this application is intended to elucidate some of the functions of these new lysyl oxidases. The role of lysyl oxidase in human disorders, either as a primary determinant of a disease process or as a secondary consequence to other genetic or environmental factors, has never been clear. By providing, for the first time, information describing the complex role of a family of lysyl oxidases in tissue structure and function, they hope to provide new and valuable insight into the precise mechanism(s) by which these critical amine oxidases influence a variety of different disease processes.

S11AR047713

2001-04-20

2007-02-28