Macrophage-stimulating protein receptor

UniProt Q04912 Organism Homo sapiens Gene MST1R, PTK8, RON EC 2.7.10.1

Also known as: MST1R, PTK8, RON

Function

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. 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. Also plays 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.

Classification

Family (Pfam): PF07714 PK_Tyr_Ser-Thr, PF01437 PSI, PF01403 Sema, PF01833 TIG
InterPro: Ig-like_fold, Ig_E-set, IPT_dom, Kinase-like_dom_sf, Plexin_repeat, Prot_kinase_dom, Protein_kinase_ATP_BS, PSI, RON_Sema, RTK, Semap_dom, Semap_dom_sf, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_HGF/MSP_rcpt, WD40/YVTN_repeat-like_dom_sf
Functional cluster: Secreted Growth Factors & Cytokines

Experimental structures · PDB · 4

3PLS X-ray 2.24A
4FWW X-ray 1.85A
4QT8 X-ray 3.00A
8ZKD X-ray 2.05A

A predicted model is available from AlphaFold.

Gene Ontology · 21

Disease associations

nasopharyngeal carcinoma, susceptibility to, 3 MONDO:0014902

Drugs targeting this protein · 3

MK-8033 inhibitor
GLESATINIB inhibitor
CRIZOTINIB inhibitor

Related proteins · sequence + function similarity

Macrophage-stimulating protein receptor 0.97
Plexin-B1 0.91
Plexin-B2 0.90
Plexin-D1 0.90
Plexin-B1 0.89
Plexin-D1 0.88
Plexin-A3 0.87
Semaphorin-4A 0.86
Plexin-A3 0.85
Semaphorin-4A 0.85
Semaphorin-4F 0.85
Plexin-B3 0.85

Co-cited proteins · studied together in the literature

Protein O-mannosyl-transferase TMEM260 1 shared papers
Protein O-mannosyl-transferase TMEM260 1 shared papers
Envelope glycoprotein 1 shared papers
Hepatocyte growth factor receptor 3 shared papers
Hyaluronidase-2 1 shared papers
Plexin-B2 1 shared papers
Plexin-B3 1 shared papers
Plexin-B1 1 shared papers
Tyrosine-protein kinase receptor Tie-1 1 shared papers
Ephrin type-A receptor 1 1 shared papers
Ephrin type-B receptor 1 1 shared papers
Ephrin type-B receptor 4 1 shared papers

Literature · 23 cited papers

The SHDRA syndrome-associated geDne TMEM260 encodes a protein-specific O-mannosyltransferase. Proc. Natl. Acad. Sci. U.S.A. · 2023
Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma. Proc. Natl. Acad. Sci. U.S.A. · 2016
Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase. PLoS ONE · 2012
Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET. J. Biol. Chem. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis. Biochemistry · 2010
The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells. Oncogene · 2009
Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res. Ther. · 2008
Patterns of somatic mutation in human cancer genomes. Nature · 2007
The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
The C terminus of RON tyrosine kinase plays an autoinhibitory role. J. Biol. Chem. · 2005
Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene · 2004
… and 11 more in the literature graph

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