Role of endoproteolytic processing in the adhesive and signaling functions of alphavbeta5 integrin.
Some integrin alpha subunits undergo a post-translational cleavage in their extracellular domain. However, the role of this cleavage in integrin function is unclear. Enzymes involved in this maturation belong to the subtilisin-like endoprotease family (convertases). To understand the role of the alpha subunit cleavage in integrin function, we have designed stable transfectants (PDX39P cells) expressing alpha(1)-PDX, a convertase inhibitor. Immunoprecipitation of cell surface proteins from PDX39P showed that alpha(3), alpha(6) and alpha(v) integrins lack endoproteolytic cleavage. We have compared adhesion between PDX39P cells and mock-transfected cells on different extracellular matrix proteins. No difference in adhesion could be observed on laminin-1 and type I collagen, while attachment of PDX39P cells to vitronectin (ligand of the alpha(v)beta(5) integrin) was dramatically reduced. 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 environment. Intracellular signaling pathways activated by alpha(v) integrin ligation 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.
Laboratoire de Biochimie Cellulaire, CNRS UPRESA 6032, Faculté de Pharmacie, 27 Bd J. Moulin, 13 385 Marseille Cedex 5, France.
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V
Berthet
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Rigot
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Champion
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J
Secchi
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F
Fouchier
J
J
Marvaldi
J
J
Luis
D000818:Animals; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D051381:Rats; D019030:Receptors, Vitronectin; D015398:Signal Transduction; D020860:Subtilisin / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
D016023:Integrins; D021122:Protein Subunits; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020860:Subtilisin