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Gene Review

MST1R  -  macrophage stimulating 1 receptor (c-met...

Homo sapiens

Synonyms: CD136, CDw136, MSP receptor, Macrophage-stimulating protein receptor, PTK8, ...
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Disease relevance of MST1R

  • We find activated RON in a subset of human bronchioloalveolar carcinoma tumors, suggesting RON involvement in this type of human lung cancer [1].
  • Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus [1].
  • In this report, we used an antibody phage display library to generate IMC-41A10, a human immunoglobulin G1 (IgG1) antibody that binds with high affinity (ED(50) = 0.15 nmol/L) to RON and effectively blocks interaction with its ligand, macrophage-stimulating protein (MSP; IC(50) = 2 nmol/L) [2].
  • The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness [3].
  • In a human gastric cancer cell line (KATO-III), we found abnormal accumulation of an uncleaved single-chain protein (delta-Ron) of 165 kDa; this molecule is encoded by a transcript differing from the full-length RON mRNA by an in-frame deletion of 49 amino acids in the beta-chain extracellular domain [4].
  • Although stimulation with HGFL had no effect on proliferation, concurrent RON receptor blockade and gemcitabine treatment increased apoptosis of RON-expressing pancreatic cancer cells versus gemcitabine treatment alone [5].

Psychiatry related information on MST1R

  • Each of them resulted in prolonged reaction times (RT) in the duration discrimination task and elicited the MMN, P3a, and RON components of the ERP [6].

High impact information on MST1R

  • MSP bound to RON on normal human bronchial epithelial cells with a high affinity (Kd = 0.5 nM) and induced autophosphorylation of RON [7].
  • 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 [7].
  • Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility [7].
  • RON, a cDNA homologous to the hepatocyte growth factor (HGF) receptor gene (MET), encodes a putative tyrosine kinase [8].
  • Here we show that the RON gene is expressed in several epithelial tissues as well as in granulocytes and monocytes [8].

Biological context of MST1R


Anatomical context of MST1R


Associations of MST1R with chemical compounds

  • Increased expression of RON and its variants resulted in colony formation and motile activities of colonic epithelial AA/C1 cells as evident in soft-agar and migration assays, respectively [15].
  • Here we present a crystal structure of the 30 kDa beta-chain of human HGFl/MSP, a serine proteinase homology domain containing the high-affinity binding site for the RON receptor [16].
  • We investigated the pathway involved in integrin-mediated RTK activation, using RON, the receptor for macrophage-stimulating protein [17].
  • Further, we show that activated RON inhibited the iNOS gene transcription activity as assessed by chloramphenicol acetyltransferase activity in Raw264.7 cells expressing RON [18].
  • Treatment of MDA MB 231 cells with mithramycin A, an inhibitor of Sp1 binding, or siRNA knock-down of Sp1 blocked RON gene expression and MSP-mediated invasion of MDA MB 231 cells [19].

Physical interactions of MST1R


Regulatory relationships of MST1R

  • HK2 produced MSP and expressed RON in a form that was phosphorylated by rMSP [21].
  • To determine the oncogenic potential of RON, transgenic mice were generated using the surfactant protein C promoter to express human wild-type RON in the distal lung epithelial cells [22].
  • One of the mechanisms of JSRV-induced cell transformation that has been proposed for epithelial cells involves JSRV Env binding Hyaluronidase 2 (the JSRV receptor), thereby inducing its degradation and allowing the release and activation of RON tyrosine kinase which is normally suppressed by HYAL-2 [23].

Other interactions of MST1R


Analytical, diagnostic and therapeutic context of MST1R


  1. Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus. Danilkovitch-Miagkova, A., Duh, F.M., Kuzmin, I., Angeloni, D., Liu, S.L., Miller, A.D., Lerman, M.I. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Therapeutic Implications of a Human Neutralizing Antibody to the Macrophage-Stimulating Protein Receptor Tyrosine Kinase (RON), a c-MET Family Member. O'toole, J.M., Rabenau, K.E., Burns, K., Lu, D., Mangalampalli, V., Balderes, P., Covino, N., Bassi, R., Prewett, M., Gottfredsen, K.J., Thobe, M.N., Cheng, Y., Li, Y., Hicklin, D.J., Zhu, Z., Waltz, S.E., Hayman, M.J., Ludwig, D.L., Pereira, D.S. Cancer Res. (2006) [Pubmed]
  3. The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Maggiora, P., Lorenzato, A., Fracchioli, S., Costa, B., Castagnaro, M., Arisio, R., Katsaros, D., Massobrio, M., Comoglio, P.M., Flavia Di Renzo, M. Exp. Cell Res. (2003) [Pubmed]
  4. A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Collesi, C., Santoro, M.M., Gaudino, G., Comoglio, P.M. Mol. Cell. Biol. (1996) [Pubmed]
  5. The RON receptor tyrosine kinase mediates oncogenic phenotypes in pancreatic cancer cells and is increasingly expressed during pancreatic cancer progression. Thomas, R.M., Toney, K., Fenoglio-Preiser, C., Revelo-Penafiel, M.P., Hingorani, S.R., Tuveson, D.A., Waltz, S.E., Lowy, A.M. Cancer Res. (2007) [Pubmed]
  6. Bottom-up influences on working memory: behavioral and electrophysiological distraction varies with distractor strength. Berti, S., Roeber, U., Schröger, E. Experimental psychology. (2004) [Pubmed]
  7. Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility. Sakamoto, O., Iwama, A., Amitani, R., Takehara, T., Yamaguchi, N., Yamamoto, T., Masuyama, K., Yamanaka, T., Ando, M., Suda, T. J. Clin. Invest. (1997) [Pubmed]
  8. RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. Gaudino, G., Follenzi, A., Naldini, L., Collesi, C., Santoro, M., Gallo, K.A., Godowski, P.J., Comoglio, P.M. EMBO J. (1994) [Pubmed]
  9. The soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation. Angeloni, D., Danilkovitch-Miagkova, A., Miagkov, A., Leonard, E.J., Lerman, M.I. J. Biol. Chem. (2004) [Pubmed]
  10. Kinases involved in MSP/RON signaling. Danilkovitch, A., Leonard, E.J. J. Leukoc. Biol. (1999) [Pubmed]
  11. RON-regulated innate immunity is protective in an animal model of multiple sclerosis. Tsutsui, S., Noorbakhsh, F., Sullivan, A., Henderson, A.J., Warren, K., Toney-Earley, K., Waltz, S.E., Power, C. Ann. Neurol. (2005) [Pubmed]
  12. The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration. Santoro, M.M., Gaudino, G., Marchisio, P.C. Dev. Cell (2003) [Pubmed]
  13. Characterization of two monoclonal antibodies against the RON tyrosine kinase receptor. Montero-Julian, F.A., Dauny, I., Flavetta, S., Ronsin, C., André, F., Xerri, L., Wang, M.H., Marvaldi, J., Breathnach, R., Brailly, H. Hybridoma (1998) [Pubmed]
  14. RON receptor tyrosine kinase, a negative regulator of inflammation, inhibits HIV-1 transcription in monocytes/macrophages and is decreased in brain tissue from patients with AIDS. Lee, E.S., Kalantari, P., Tsutsui Section, S., Klatt, A., Holden, J., Correll, P.H., Power Section, C., Henderson, A.J. J. Immunol. (2004) [Pubmed]
  15. RNA-mediated gene silencing of the RON receptor tyrosine kinase alters oncogenic phenotypes of human colorectal carcinoma cells. Xu, X.M., Wang, D., Shen, Q., Chen, Y.Q., Wang, M.H. Oncogene (2004) [Pubmed]
  16. Crystal structure of the beta-chain of human hepatocyte growth factor-like/macrophage stimulating protein. Carafoli, F., Chirgadze, D.Y., Blundell, T.L., Gherardi, E. FEBS J. (2005) [Pubmed]
  17. Integrin-mediated RON growth factor receptor phosphorylation requires tyrosine kinase activity of both the receptor and c-Src. Danilkovitch-Miagkova, A., Angeloni, D., Skeel, A., Donley, S., Lerman, M., Leonard, E.J. J. Biol. Chem. (2000) [Pubmed]
  18. Activation of the RON receptor tyrosine kinase inhibits inducible nitric oxide synthase (iNOS) expression by murine peritoneal exudate macrophages: phosphatidylinositol-3 kinase is required for RON-mediated inhibition of iNOS expression. Chen, Y.Q., Fisher, J.H., Wang, M.H. J. Immunol. (1998) [Pubmed]
  19. Regulation of RON tyrosine kinase-mediated invasion of breast cancer cells. Thangasamy, A., Rogge, J., Ammanamanchi, S. J. Biol. Chem. (2008) [Pubmed]
  20. Requirement of phosphatidylinositol-3 kinase for epithelial cell migration activated by human macrophage stimulating protein. Wang, M.H., Montero-Julian, F.A., Dauny, I., Leonard, E.J. Oncogene (1996) [Pubmed]
  21. Macrophage-stimulating protein is produced by tubular cells and activates mesangial cells. Rampino, T., Collesi, C., Gregorini, M., Maggio, M., Soccio, G., Guallini, P., Dal Canton, A. J. Am. Soc. Nephrol. (2002) [Pubmed]
  22. Multiple pulmonary adenomas in the lung of transgenic mice overexpressing the RON receptor tyrosine kinase. Recepteur d'origine nantais. Chen, Y.Q., Zhou, Y.Q., Fu, L.H., Wang, D., Wang, M.H. Carcinogenesis (2002) [Pubmed]
  23. Association of RON tyrosine kinase with the Jaagsiekte sheep retrovirus envelope glycoprotein. Varela, M., Chow, Y.H., Sturkie, C., Murcia, P., Palmarini, M. Virology (2006) [Pubmed]
  24. HGF controls branched morphogenesis in tubular glands. Maffè, A., Comoglio, P.M. European journal of morphology. (1998) [Pubmed]
  25. Biological aspects of macrophage-stimulating protein (MSP) and its receptor. Leonard, E.J. Ciba Found. Symp. (1997) [Pubmed]
  26. Collaborative activities of macrophage-stimulating protein and transforming growth factor-beta1 in induction of epithelial to mesenchymal transition: roles of the RON receptor tyrosine kinase. Wang, D., Shen, Q., Chen, Y.Q., Wang, M.H. Oncogene (2004) [Pubmed]
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