Role of endoproteolytic processing in the adhesive and signaling functionsof alpha(v)beta(5) integrin

Some integrin alpha subunits undergo a post-translational cleavage in their extracellular domain. However, the role of this cleavage in integrin funct ion is unclear. Enzymes involved in this maturation belong to the subtilisi n-like endoprotease family (convertases). To understand the role of the alp ha subunit cleavage in integrin function, we have designed stable transfect ants (PDX39P cells) expressing alpha (1)-PDX, a convertase inhibitor. Immun oprecipitation of cell surface proteins from PDX39P showed that alpha (3), alpha (6) and alpha (v) integrins lack endoproteolytic cleavage. We have co mpared adhesion between PDX39P cells and mock-transfected cells on differen t extracellular matrix proteins. No difference in adhesion could be observe d on laminin-l and type I collagen, while attachment of PDX39P cells to vit ronectin (ligand of the alpha (v)beta (5) integrin) was dramatically reduce d. The reduced adhesion of PDX39P cells was not due to changes in integrin affinity as determined by solid-phase receptor assay in a cell-free environ ment. Intracellular signaling pathways activated by alpha (v) integrin liga tion were also affected in PDX39P cells. It thus seems that the absence of endoproteolytic cleavage of alpha (v) integrins has important consequences on signal transduction pathways leading to alterations in integrin function such as cell adhesion.