Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility

Osamu Sakamoto, Atsushi Iwama, Ryoichi Amitani, Toyohiro Takehara, Naoto Yamaguchi, Taro Yamamoto, Keisuke Masuyama, Tohru Yamanaka, Masayuki Ando, Toshio Suda

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Abstract

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 (K(d) = 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.

Original languageEnglish
Pages (from-to)701-709
Number of pages9
JournalJournal of Clinical Investigation
Volume99
Issue number4
DOIs
Publication statusPublished - 1997 Feb 15

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Keywords

  • RON
  • ciliary motility
  • ciliated epithelium
  • macrophage-stimulating protein
  • receptor tyrosine kinase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sakamoto, O., Iwama, A., Amitani, R., Takehara, T., Yamaguchi, N., Yamamoto, T., Masuyama, K., Yamanaka, T., Ando, M., & Suda, T. (1997). Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility. Journal of Clinical Investigation, 99(4), 701-709. https://doi.org/10.1172/JCI119214