title: Activation of macrophage-stimulating protein by human airway trypsin-like protease.
abstract: Macrophage-stimulating protein (MSP) circulates as a proform protein and requires proteolytic processing for activation. Respiratory ciliated cells express the MSP receptor, recepteur d'origine nantais (RON), at the apical surface, which reportedly has an important role in ciliary function. Like RON, human airway trypsin-like protease (HAT) is also expressed at the apical surface of ciliated cells. Here we show that HAT cleaves proMSP at the physiological activation site, Arg483-Val484. MSP processed by HAT could induce chemotactic responses and morphological changes of peritoneal macrophages. In human respiratory epithelial cells, knock down of HAT expression reduced proMSP processing and RON autophosphorylation. We suggest that HAT is important for MSP-RON signaling in the respiratory tract.
authors.affiliation: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Orikawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Baba
authors.forename: Kenji
authors.initials: K
authors.lastname: Yorita
authors.forename: Sumio
authors.initials: S
authors.lastname: Sakoda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011498:Protein Precursors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D012697:Serine Endopeptidases; C112256:human airway trypsin-like protease