title: The major excreted protein of transformed fibroblasts is an activable acid-protease.
abstract: Malignant transformation of mouse cells by a variety of agents or treatment with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate or platelet-derived growth factor results in increased synthesis and secretion of a 39,000-dalton protein termed major excreted protein (MEP). We report here that secreted MEP is an acid-activable protease. The secreted precursor form of the protease is auto-activated at low pH and is able to digest a variety of proteins, including the extracellular matrix proteins fibronectin, collagen, and laminin. MEP protease activity has pH optimum of 3.3-3.6 and is temperature- and concentration-dependent. The activity is inhibited by sulfhydryl protease inhibitors such as leupeptin and iodoacetic acid and not by metallo-, seryl-, or carboxyprotease inhibitors. The MEP-derived protease has characteristics distinct from the cathepsins previously reported and thus may be a new acid-protease of mouse cells.
mesh_terms: D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000302:isolation & purification* / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000201:enzymology* / Q000378:metabolism; D002472:Cell Transformation, Viral; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000302:isolation & purification* / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007708:Kirsten murine sarcoma virus; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D009363:Neoplasm Proteins / Q000302:isolation & purification* / Q000378:metabolism; D011498:Protein Precursors / Q000302:isolation & purification* / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D009363:Neoplasm Proteins; D011498:Protein Precursors; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse