Cleavage of β4 integrin by matrilysin

Overexpression of the matrix metalloproteinase matrilysin and the absence of β4 integrin are two features characteristic of human prostate carcinoma. In the following study we demonstrate that the β4 integrin, but not the α6 or β1 integrin subunits, is cleaved by matrilysin in vitro. A specific fragment of 90 kDa is generated using matrilysin, which is not observed with other proteases. Two putative cleavage sites for matrilysin within the extracellular domain of the β4 integrin at residues 107 (isoleucine, prior to the ligand-binding region) and 417 (leucine, prior to cysteine-rich region) are identified by sequence comparisons with known matrilysin substrates. The selective cleavage of the β4 integrin by matrilysin may partly explain the loss of β4 integrin expression in invasive prostate carcinoma.