Cleavage of beta 4 integrin by matrilysin.
Overexpression of the matrix metalloproteinase matrilysin and the absence of beta 4 integrin are two features characteristic of human prostate carcinoma. In the following study we demonstrate that the beta 4 integrin, but not the alpha 6 or beta 1 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 beta 4 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 beta 4 integrin by matrilysin may partly explain the loss of beta 4 integrin expression in invasive prostate carcinoma.
von Bredow
D C
DC
Department of Pathology, University of Arizona, Tucson 85724, USA.
Nagle
R B
RB
Bowden
G T
GT
Cress
A E
AE
D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D002154:Calpain / Q000378:metabolism / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D039663:Integrin beta4; D016023:Integrins / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000378:metabolism* / Q000494:pharmacology*; D011471:Prostatic Neoplasms; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D014357:Trypsin / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology
D015703:Antigens, CD; D000954:Antigens, Surface; D016326:Extracellular Matrix Proteins; D039663:Integrin beta4; D016023:Integrins; D014357:Trypsin; D002154:Calpain; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7