Macrophage-stimulating protein (MSP) is an 80-kD serum protein with homology to hepatocyte growth factor (HGF). Its receptor, RON tyrosine kinase, is a new member of the HGF receptor family. The MSP-RON signaling pathway has been implicated in the functional regulation of mononuclear phagocytes. However, the function of this pathway in other types of cells has not been elucidated. Here we show that in contrast to the HGF receptor, which was expressed at the basolateral surface, RON was localized at the apical surface of ciliated epithelia in the airways and oviduct. In addition, MSP was found in the bronchoalveolar space at biologically significant concentrations. MSP bound to RON on normal human bronchial epithelial cells with a high affinity (Kd = 0.5 nM) and induced autophosphorylation of RON. Activation of RON by MSP led to a significant increase in ciliary beat frequency of human nasal cilia. These findings indicate that the ciliated epithelium of the mucociliary transport apparatus is a novel target of MSP. Ciliary motility is critical for mucociliary transport. Our findings suggest that the MSP-RON signaling pathway is a novel regulatory system of mucociliary function and might be involved in the host defense and fertilization.
O Sakamoto, A Iwama, R Amitani, T Takehara, N Yamaguchi, T Yamamoto, K Masuyama, T Yamanaka, M Ando, T Suda
Title and authors | Publication | Year |
---|---|---|
Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis
Retuerto-Guerrero M, López-Medrano R, de Freitas-González E, Rivero-Lezcano OM |
Microorganisms | 2024 |
An Introduction and Overview of RON Receptor Tyrosine Kinase Signaling
Hunt BG, Fox LH, Davis JC, Jones A, Lu Z, Waltz SE |
Genes & development | 2023 |
Identification of prognostic hub genes and therapeutic targets for selenium deficiency in chicks model through transcriptome profiling.
Lingamgunta LK, Aloor BP, Dasari S, Ramakrishnan R, Botlagunta M, Madikonda AK, Gopal S, Sade A |
Scientific Reports | 2023 |
USP28 enables oncogenic transformation of respiratory cells and its inhibition potentiates targeted molecular therapy
Cristian Prieto-Garcia, Oliver Hartmann, Michaela Reissland, Fabian Braun, Süleiman Bozkurt, Carmina Fuss, Christina Schülein-Völk, Alexander Buchberger, Marco A. Calzado, Mathias Rosenfeldt, Ivan Dikic, Christian Münch, Markus Diefenbacher |
Molecular Oncology | 2022 |
Mycobacterium abscessus: It's Complex.
Abdelaal HFM, Chan ED, Young L, Baldwin SL, Coler RN |
Microorganisms | 2022 |
Inhibition of USP28 overcomes Cisplatin-resistance of squamous tumors by suppression of the Fanconi anemia pathway
C Prieto-Garcia, O Hartmann, M Reissland, T Fischer, CR Maier, M Rosenfeldt, C Schülein-Völk, K Klann, R Kalb, I Dikic, C Münch, ME Diefenbacher |
Cell Death and Differentiation | 2021 |
Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease
K Kumar, OM Kon |
Microorganisms | 2021 |
Novel Tyrosine Phosphorylation Signals in the Nucleus and on Mitotic Spindle Fibers and Lysosomes Revealed by Strong Inhibition of Tyrosine Dephosphorylation
N Yamaguchi |
YAKUGAKU ZASSHI | 2021 |
MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity
L Huang, X Fang, D Shi, S Yao, W Wu, Q Fang, H Yao |
Frontiers in immunology | 2020 |
Ligand‐based Discovery of Novel Small Molecule Inhibitors of RON Receptor Tyrosine Kinase
O Zarei, N Faham, H Vankayalapati, SL Raeppel, AL Welm, M HamzehMivehroud |
Molecular Informatics | 2020 |
Redox regulation of motile cilia in airway disease
ME Price, JH Sisson |
Redox Biology | 2019 |
Assessment of fine particles released during paper printing and shredding processes
N Shin, K Velmurugan, C Su, AK Bauer, CS Tsai |
ENVIRON SCI-PROC IMP | 2019 |
Acquired and genetic host susceptibility factors and microbial pathogenic factors that predispose to nontuberculous mycobacterial infections
JR Honda, S Alper, X Bai, ED Chan |
Current Opinion in Immunology | 2018 |
Identification of the splice variants of Recepteur d'Origine nantais (RON) in lung cancer cell lines
S Krishnaswamy, I Bukhari, AK Mohammed, OE Amer, G Tripathi, MS Alokail, NM Al-Daghri |
Gene | 2018 |
Nontuberculous Mycobacterial Disease: A Comprehensive Approach to Diagnosis and Management
DE Griffith |
2018 | |
Involvement of c-Jun N-Terminal Kinase in TNF-α–Driven Remodeling
IM Eurlings, NL Reynaert, C de Wetering, SW Aesif, EM Mercken, R Cabo, JL van der Velden, YM Janssen-Heininger, EF Wouters, MA Dentener |
American journal of respiratory cell and molecular biology | 2017 |
Human airway trypsin-like protease, a serine protease involved in respiratory diseases
A Menou, JW Duitman, P Flajolet, JM Sallenave, AA Mailleux, B Crestani |
American journal of physiology. Lung cellular and molecular physiology | 2017 |
Splice variants of the extracellular region of RON receptor tyrosine kinase in lung cancer cell lines identified by PCR and sequencing
S Krishnaswamy, AK Mohammed, G Tripathi, MS Alokail, NM Al-Daghri |
BMC Cancer | 2017 |
Susceptibility genes for nontuberculous mycobacterial disease
H NAMKOONG, N HASEGAWA, T BETSUYAKU |
Japanese Journal of Clinical Immunology | 2017 |
Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery
O Zarei, S Benvenuti, F Ustun-Alkan, M Hamzeh-Mivehroud, S Dastmalchi |
Journal of Cancer Research and Clinical Oncology | 2016 |
Genome-wide analysis identifies 12 loci influencing human reproductive behavior
N Barban, R Jansen, R Vlaming, A Vaez, JJ Mandemakers, FC Tropf, X Shen, JF Wilson, DI Chasman, IM Nolte, V Tragante, SW van der Laan, JR Perry, A Kong, TS Ahluwalia, E Albrecht, L Yerges-Armstrong, G Atzmon, K Auro, K Ayers, A Bakshi, D Ben-Avraham, K Berger, A Bergman, L Bertram, LF Bielak, G Bjornsdottir, MJ Bonder, L Broer, M Bui, C Barbieri, A Cavadino, JE Chavarro, C Turman, MP Concas, HJ Cordell, G Davies, P Eibich, N Eriksson, T Esko, J Eriksson, F Falahi, JF Felix, MA Fontana, L Franke, I Gandin, AJ Gaskins, C Gieger, EP Gunderson, X Guo, C Hayward, C He, E Hofer, H Huang, PK Joshi, S Kanoni, R Karlsson, S Kiechl, A Kifley, A Kluttig, P Kraft, V Lagou, C Lecoeur, J Lahti, R Li-Gao, PA Lind, T Liu, E Makalic, C Mamasoula, L Matteson, H Mbarek, PF McArdle, G McMahon, SF Meddens, E Mihailov, M Miller, SA Missmer, C Monnereau, PJ van der Most, R Myhre, MA Nalls, T Nutile, IP Kalafati, E Porcu, I Prokopenko, KB Rajan, J Rich-Edwards, CA Rietveld, A Robino, LM Rose, R Rueedi, KA Ryan, Y Saba, D Schmidt, JA Smith, L Stolk, E Streeten, A Tönjes, G Thorleifsson, S Ulivi, J Wedenoja, J Wellmann, P Willeit, J Yao, L Yengo, JH Zhao, W Zhao, DV Zhernakova, N Amin, H Andrews, B Balkau, N Barzilai, S Bergmann, G Biino, H Bisgaard, K Bønnelykke, DI Boomsma, JE Buring, H Campbell, S Cappellani, M Ciullo, SR Cox, F Cucca, D Toniolo, G Davey-Smith, IJ Deary, G Dedoussis, P Deloukas, CM van Duijn, EJ de Geus, JG Eriksson, DA Evans, JD Faul, CF Sala, P Froguel, P Gasparini, G Girotto, HJ Grabe, KH Greiser, PJ Groenen, HG de Haan, J Haerting, TB Harris, AC Heath, K Heikkilä, A Hofman, G Homuth, EG Holliday, J Hopper, E Hyppönen, B Jacobsson, VW Jaddoe, M Johannesson, A Jugessur, M Kähönen, E Kajantie, SL Kardia, B Keavney, I Kolcic, P Koponen, P Kovacs, F Kronenberg, Z Kutalik, ML Bianca, G Lachance, WG Iacono, S Lai, T Lehtimäki, DC Liewald, CM Lindgren, Y Liu, R Luben, M Lucht, R Luoto, P Magnus, PK Magnusson, NG Martin, M McGue, R McQuillan, SE Medland, C Meisinger, D Mellström, A Metspalu, M Traglia, L Milani, P Mitchell, GW Montgomery, D Mook-Kanamori, R Mutsert, EA Nohr, C Ohlsson, J Olsen, KK Ong, L Paternoster, A Pattie, BW Penninx, M Perola, PA Peyser, M Pirastu, O Polasek, C Power, J Kaprio, LJ Raffel, K Räikkönen, O Raitakari, PM Ridker, SM Ring, K Roll, I Rudan, D Ruggiero, D Rujescu, V Salomaa, D Schlessinger, H Schmidt, R Schmidt, N Schupf, J Smit, R Sorice, TD Spector, JM Starr, D Stöckl, K Strauch, M Stumvoll, MA Swertz, U Thorsteinsdottir, AR Thurik, NJ Timpson, JY Tung, AG Uitterlinden, S Vaccargiu, J Viikari, V Vitart, H Völzke, P Vollenweider, D Vuckovic, J Waage, GG Wagner, JJ Wang, NJ Wareham, DR Weir, G Willemsen, J Willeit, AF Wright, KT Zondervan, K Stefansson, RF Krueger, JJ Lee, DJ Benjamin, D Cesarini, PD Koellinger, M Hoed, H Snieder, MC Mills |
Nature Genetics | 2016 |
Novel splicing variants of recepteur d'origine nantais (RON) tyrosine kinase involving exons 15–19 in lung cancer
S Krishnaswamy, AK Mohammed, OE Amer, G Tripathi, MS Alokail, NM Al-Daghri |
Lung Cancer | 2016 |
Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis
M Song, Y He, H Zhou, Y Zhang, X Li, Y Yu |
Scientific Reports | 2016 |
Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma
W Dai, H Zheng, AK Cheung, CS Tang, JM Ko, BW Wong, MM Leong, PC Sham, F Cheung, DL Kwong, RK Ngan, WT Ng, CC Yau, J Pan, X Peng, S Tung, Z Zhang, M Ji, AK Chiang, AW Lee, VH Lee, KO Lam, KH Au, HC Cheng, HH Yiu, ML Lung |
Proceedings of the National Academy of Sciences | 2016 |
Evolutionary Biology
R Kammerer, F Herse, W Zimmermann |
Evolutionary Biology | 2016 |
MST1R mutation as a genetic cause of Lady Windermere syndrome
KL Becker, P Arts, M Jaeger, TS Plantinga, C Gilissen, A van Laarhoven, J van Ingen, JA Veltman, LA Joosten, A Hoischen, MG Netea, MD Iseman, ED Chan, FL van de Veerdonk |
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology | 2016 |
Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease
EP Szymanski, JM Leung, CJ Fowler, C Haney, AP Hsu, F Chen, P Duggal, AJ Oler, R McCormack, E Podack, RA Drummond, MS Lionakis, SK Browne, DR Prevots, M Knowles, G Cutting, X Liu, SE Devine, CM Fraser, H Tettelin, KN Olivier, SM Holland |
American journal of respiratory and critical care medicine | 2015 |
Roles of macrophage stimulating protein and tyrosine kinase receptor RON in smoke-induced airway inflammation of rats
Tao Wang, Xiaoju Chen, Wenbo Zhang, Xiaojun Xiang, Changyan Leng, Qinyao Jia |
International journal of clinical and experimental pathology | 2015 |
Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas
EV de Laar, M Clifford, S Hasenoeder, BR Kim, D Wang, S Lee, J Paterson, NM Vu, TK Waddell, S Keshavjee, MS Tsao, L Ailles, N Moghal |
Respiratory Research | 2014 |
The Effect of Drugs and Other Compounds on the Ciliary Beat Frequency of Human Respiratory Epithelium
AD Workman, NA Cohen |
American journal of rhinology & allergy | 2014 |
Cigarette Smoke Extract Induces a Phenotypic Shift in Epithelial Cells; Involvement of HIF1α in Mesenchymal Transition
IM Eurlings, NL Reynaert, T Beucken, HR Gosker, CC de Theije, FM Verhamme, KR Bracke, EF Wouters, MA Dentener, O Eickelberg |
PloS one | 2014 |
Activation of Macrophage-stimulating Protein by Human Airway Trypsin-like Protease
H Orikawa, M Kawaguchi, T Baba, K Yorita, S Sakoda, H Kataoka |
FEBS Letters | 2012 |
Differential expression of RON in small and non-small cell lung cancers
R Kanteti, S Krishnaswamy, D Catenacci, YH Tan, E EL-Hashani, G Cervantes, AN Husain, M Tretiakova, EE Vokes, H Huet, R Salgia |
Genes Chromosomes and Cancer | 2012 |
Prostate transglutaminase: a unique transglutaminase and its role in prostate cancer
WG Jiang, RJ Ablin |
Biomarkers in Medicine | 2011 |
Advances in Cancer Research
M Lemaire, S Deleu, ED Bruyne, EV Valckenborgh, E Menu, K Vanderkerken |
Advances in Cancer Research Volume 110 | 2011 |
RON RECEPTOR TYROSINE KINASE NEGATIVELY REGULATES TNFα PRODUCTION IN ALVEOLAR MACROPHAGES BY INHIBITING NF-κB ACTIVITY AND ADAM17 PRODUCTION
NM Nikolaidis, JK Gray, D Gurusamy, W Fox, WD Stuart, N Huber, SE Waltz |
Shock | 2010 |
The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment
TM Antalis, MS Buzza, KM Hodge, JD Hooper, S Netzel‑Arnett |
Biochemical Journal | 2010 |
Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus
PR Shea, K Virtaneva, JJ 3rd, SF Porcella, WT Barry, FA Wright, SD Kobayashi, A Carmody, RM Ireland, DE Sturdevant, SM Ricklefs, I Babar, CA Johnson, MR Graham, DJ Gardner, JR Bailey, MJ Parnell, FR Deleo, JM Musser |
Proceedings of the National Academy of Sciences | 2010 |
Transactivation of RON receptor tyrosine kinase by interaction with PDGF receptor beta during steady-state growth of human mesangial cells
T Kobayashi, Y Furukawa, J Kikuchi, C Ito, Y Miyata, S Muto, A Tanaka, E Kusano |
Kidney international. Supplement | 2009 |
Protein levels of CC chemokine ligand (CCL)15, CCL16 and macrophage stimulating protein in patients with sarcoidosis
A Arakelyan, E Kriegova, Z Kubistova, F Mrazek, M Kverka, RM du Bois, V Kolek, M Petrek |
Clinical & Experimental Immunology | 2009 |
Scatter Factors in renal disease: Dr. Jeckyll and Mr. Hyde?
T Rampino, M Gregorini, AD Canton |
Cytokine & Growth Factor Reviews | 2009 |
The role of NKT cells in tumor immunity
M Terabe, JA Berzofsky |
Advances in cancer research | 2008 |
Apical oxidative hyaluronan degradation stimulates airway ciliary beating via RHAMM and RON
D Manzanares, ME Monzon, RC Savani, M Salathe |
American journal of respiratory cell and molecular biology | 2007 |
Regulation of Mammalian Ciliary Beating
M Salathe |
Annual Review of Physiology | 2007 |
Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release and NF-kappaB pathway
G Gunella, C Bardelli, A Amoruso, I Viano, P Balbo, S Brunelleschi |
British Journal of Pharmacology | 2006 |
Repression of the MSP/MST-1 gene contributes to the antiapoptotic gain of function of mutant p53
A Zalcenstein, L Weisz, P Stambolsky, J Bar, V Rotter, M Oren |
Oncogene | 2005 |
Macrophage-Stimulating Protein Promotes Hair Growth Ex Vivo and Induces Anagen from Telogen Stage Hair Follicles In Vivo
KJ McElwee, A Huth, S Kissling, R Hoffmann |
Journal of Investigative Dermatology | 2004 |
Characterization of a single-chain intrabody directed against the human receptor tyrosine kinase Ron
P Secco, M Ferretti, D Gioia, P Cesaro, C Bozzo, JD Marks, C Santoro |
Journal of Immunological Methods | 2004 |
Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus
A Danilkovitch-Miagkova, FM Duh, I Kuzmin, D Angeloni, SL Liu, AD Miller, MI Lerman |
Proceedings of the National Academy of Sciences | 2003 |
The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxide synthase levels and ovulation
KA Hess, SE Waltz, K Toney-Earley, SJ Degen |
Fertility and Sterility | 2003 |
Cross-talk between the receptor tyrosine kinases Ron and epidermal growth factor receptor
BE Peace, KJ Hill, SJ Degen, SE Waltz |
Experimental Cell Research | 2003 |
Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase
MH Wang, D Wang, YQ Chen |
Carcinogenesis | 2003 |
Analysis of RON receptor tyrosine kinase and its splicing variant in malignant and non-malignant human colonic mucosa
T Okino, H Egami, H Ohmachi, E Takai, Y Tamori, K Nakagawa, S Nakano, J Akagi, O Sakamoto, T Suda, M Ogawa |
International Congress Series | 2003 |
Lung Biology in Health and Disease
N Zamel |
Lung Biology in Health and Disease: Experimental Models and Therapeutic Potential | 2003 |
Receptor Tyrosine Kinase Ron Is Expressed in Mouse Reproductive Tissues During Embryo Implantation and Is Important in Trophoblast Cell Function1
KA Hess, SE Waltz, EL Chan, SJ Degen |
Biology of reproduction | 2003 |
Redistribution of ERK/MAP kinase to uropod-like structures in interleukin-3-induced cell shape changes
A Mera, M Suga, Y Nakayama, M Ando, T Suda, N Yamaguchi |
Immunology Letters | 2002 |
The Role of the Receptor Tyrosine Kinase Ron in Nickel-Induced Acute Lung Injury
SA McDowell, A Mallakin, CJ Bachurski, K Toney-Earley, DR Prows, T Bruno, KH Kaestner, DP Witte, H Melin-Aldana, SJ Degen, GD Leikauf, SE Waltz |
American journal of respiratory cell and molecular biology | 2002 |
Targeted expression of the receptor tyrosine kinase RON in distal lung epithelial cells results in multiple tumor formation: oncogenic potential of RON in vivo
YQ Chen, YQ Zhou, JH Fisher, MH Wang |
Oncogene | 2002 |
Macrophage stimulating protein (MSP) evokes superoxide anion production by human macrophages of different origin
S Brunelleschi, L Penengo, L Lavagno, C Santoro, D Colangelo, I Viano, G Gaudino |
British Journal of Pharmacology | 2001 |
Results from a Genome-wide Search for Predisposing Genes in Sarcoidosis
M Schürmann, P Reichel, B Müller-Myhsok, M Schlaak, J Müller-Quernheim, E Schwinger |
American journal of respiratory and critical care medicine | 2001 |
Immunohistochemical analysis of distribution of RON receptor tyrosine kinase in human digestive organs
T Okino, H Egami, H Ohmachi, E Takai, Y Tamori, A Nakagawa, S Nakano, O Sakamoto, T Suda, M Ogawa |
Digestive Diseases and Sciences | 2001 |
Elevated levels of macrophage-stimulating protein in induced sputum of patients with bronchiectasis
Y Takano, O Sakamoto, M Suga, T Suda, M Ando |
Respiratory Medicine | 2000 |
Characterization of Free α- and β-Chains of Recombinant Macrophage-Stimulating Protein
W Yoshikawa, H Hara, T Takehara, M Shimonishi, H Sakai, N Shimizu, S Shimizu, MH Wang, M Hagiya, A Skeel, EJ Leonard |
Archives of Biochemistry and Biophysics | 1999 |
Induction of Cell Shape Changes through Activation of the Interleukin-3 Common β Chain Receptor by the RON Receptor-type Tyrosine Kinase
A Mera, M Suga, M Ando, T Suda, N Yamaguchi |
The Journal of biological chemistry | 1999 |
Characterization of Two Monoclonal Antibodies Against the RON Tyrosine Kinase Receptor
F Montero-Julian, I Dauny, S Flavetta, C Ronsin, F André, L Xerri, M Wang, J Marvaldi, R Breathnach, H Brailly |
Hybridoma | 1998 |
Interactions between scatter factors and their receptors: hints for therapeutic applications
L Trusolino, L Pugliese, PM Comoglio |
The FASEB Journal | 1998 |
Macrophage Stimulating Protein (MSP) Binds to Its Receptor via the MSP β Chain
MH Wang, FM Julian, R Breathnach, PJ Godowski, T Takehara, W Yoshikawa, M Hagiya, EJ Leonard |
The Journal of biological chemistry | 1997 |