MSP1R

Synonyms

EC 2.7.10.1, Protein-Tyrosine Kinase 8, RON, Macrophage-Stimulating Protein Receptor, SEA, S13 Erythroblastosis Oncogene Homolog, S13 Erythroblastosis (Avian) Oncogene Homolog, Macrophage Stimulating 1 Receptor, PTK8 Protein Tyrosine Kinase 8, S13 Avian Erythroblastosis Oncogene Homolog, MST1R, NPCA3, CD136 Antigen, C-Met-Related Tyrosine Kinase, CD136, CDw136, PTK8, P185-Ron, EC:2.7.10.1, MSP Receptor, EC 2.7.10

Description

Macrophage-stimulating protein receptor is a protein that in humans is encoded by the MST1R gene. MST1R is also known as RON (Recepteur d'Origine Nantais) kinase, named after the French city in which it was discovered. It is related to the c-MET receptor tyrosine kinase. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.

KO Status

RenMab: F2 (-/-)

Drug Information

Launched drug: 1
Drugs in clinical trials: 5
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Crizotinib

PF-1066, PF-2341066, PF-02341066, PF-002341066

Approved

Pfizer Pharmaceuticals Ltd (China)

Kidney Diseases, Lung Neoplasms, Lymphoma, Large-Cell, Anaplastic, Carcinoma, Non-Small-Cell Lung

TQ-B3139

TQ-B3139

Phase 3 Clinical

Jiangsu Chia Tai-Tianqing Pharmaceutical Co Ltd, Beijing Sailintai Medicine Technology Co Ltd

Solid tumours, Carcinoma, Non-Small-Cell Lung

ASLAN-002

ASLAN-002, BMS-777607, BMS-797669

Phase 2 Clinical

Bristol-Myers Squibb Company

Solid tumours, Stomach Neoplasms, Breast Neoplasms

Glesatinib

MG-90265, MGCD-265, MG-90265X, 7Q29OXD98N, MG-90265H9, MG-90265gly

Phase 2 Clinical

Mirati Therapeutics

Carcinoma, Non-Small-Cell Lung

Ningetinib Tosylate

CT-053, CT-053-PTSA

Phase 2 Clinical

Hec Pharm Co Ltd

Solid tumours, Intestinal Neoplasms, Stomach Neoplasms, Carcinoma, Renal Cell, Leukemia, Myeloid, Acute, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Hepatocellular

AL-2846

AL-2846

Phase 2 Clinical

Advenchen Laboratories Nanjing Ltd, Jiangsu Chia Tai-Tianqing Pharmaceutical Co Ltd

Bone metastases, Liver Neoplasms, Stomach Neoplasms, Pancreatic Neoplasms, Neurofibroma, Prostatic Neoplasms, Medullary thyroid cancer (MTC), Colorectal Neoplasms, Glioma, Carcinoma, Non-Small-Cell Lung, Neurofibromatosis 1

Narnatumab

Discontinued

Eli Lilly And Company

Neoplasms

References


Title

Authors

Source

A novel putative receptor protein tyrosine kinase of the met family

Ronsin C., Muscatelli F., Mattei M.-G., Breathnach R.,

Oncogene 8:1195-1202(1993)

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. 16:5518-5526(1996)

Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis

Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.,

Arthritis Res. Ther. 10:R73-R73(2008)

The DNA sequence, annotation and analysis of human chromosome 3

Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Gibbs R.A.,

Nature 440:1194-1198(2006)

A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor

Ponzetto C., Bardelli A., Maina F., Longati P., Panayotou G., Dhand R., Waterfield M.D., Comoglio P.M.,

Mol. Cell. Biol. 13:4600-4608(1993)

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. 13:3524-3532(1994)

Identification of the ron gene product as the receptor for the human macrophage stimulating protein

Wang M.-H., Ronsin C., Gesnel M.-C., Coupey L., Skeel A., Leonard E.J., Breatnach R.,

Science 266:117-119(1994)

Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury

Nanney L.B., Skeel A., Luan J., Polis S., Richmond A., Wang M.H., Leonard E.J.,

J. Invest. Dermatol. 111:573-581(1998)

Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism

Danilkovitch A., Skeel A., Leonard E.J.,

Exp. Cell Res. 248:575-582(1999)

Interaction of macrophage-stimulating protein with its receptor. Residues critical for beta chain binding and evidence for independent alpha chain binding

Danilkovitch A., Miller M., Leonard E.J.,

J. Biol. Chem. 274:29937-29943(1999)