Toggle navigation
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
About
What is Reactome ?
News
Team
Scientific Advisory Board
Funding
Editorial Calendar
Release Calendar
Statistics
Our Logo
License Agreement
Privacy Notice
Disclaimer
Digital Preservation
Contact us
Content
Table of Contents
DOIs
Data Schema
Reactome Research Spotlight
ORCID Integration Project
COVID-19 Disease Pathways
Docs
Userguide
Pathway Browser
How do I search ?
Details Panel
Analysis Tools
Analysis Data
Analysis Gene Expression
Species Comparison
Tissue Distribution
Diseases
Cytomics
Review Status of Reactome Events
ReactomeFIViz
Developer's Zone
Graph Database
Analysis Service
Content Service
Pathways Overview
Pathway Diagrams
Icon Info
EHLD Specs & Guidelines
Icon Library Guidelines
Data Model
Curator Guide
Release Documentation
Computationally inferred events
FAQ
Linking to Us
Citing us
Tools
Pathway Browser
Analyse gene list
Analyse gene expression
Species Comparison
Tissue Distribution
Analysis Service
Content Service
ReactomeFIViz
Advanced Data Search
Site Search
Community
Contribute Pathway Knowledge
Icon Library
Outreach
Events
Publications
Partners
Contributors
Resources Guide
Download
Search ...
Go!
Signaling by MST1
Stable Identifier
R-HSA-8852405
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
Signal Transduction (Homo sapiens)
Signaling by Receptor Tyrosine Kinases (Homo sapiens)
Signaling by MST1 (Homo sapiens)
General
SBML
|
BioPAX
Level 2
Level 3
|
PDF
SVG
|
PNG
Low
Medium
High
|
PPTX
|
SBGN
Click the image above or
here
to open this pathway in the Pathway Browser
Inflammatory mediators such as growth factors produced by macrophages play an important role in the inflammatory response occurring during bacterial infection, tissue injury and immune responses. Many growth factors and their receptor-type protein tyrosine kinases (RTKs) play a critical role in inflammation, wound healing and tissue remodelling. The growth factor hepatocyte growth factor-like protein (MST1, also known as macrophage-stimulating protein, MSP) binds to a specific receptor, macrophage-stimulating protein receptor (MST1R, also known as RON, recepteur d'origine nantais). MST1 belongs to the kringle protein family, which includes HGF and plasminogen. It is produced by the liver and circulates in the blood as a biologically-inactive single chain precursor (pro-MST1). Proteolytic cleavage of pro-MST1 into the biologically-active MST1 dimer is necessary for receptor binding. Cleavage occurs during blood coagulation and at inflammatory sites, the resultant MST1 dimer then binds MST1R receptors on local macrophages. MST1R is ubiquitously expressed but mainly in epithelial cells.
MST1 binding to MST1R promotes receptor homodimerisation which in turn allows autophosphorylation of two tyrosine residues within the catalytic site which regulates kinase activity and allows phosphorylation of the carboxy-terminal binding site of the receptor. The docking site is essential for downstream signaling through direct and indirect binding of SH2 domain-containing adaptor proteins such as GRB2, PI3K, and SRC. MST1/MST1R signaling plays a dual role in regulating inflammation; initially stimulating chemotaxis and phagocytosis (macrophage activation) and then exerts broad inhibitory effects on macrophages, limiting the extent of inflammtory responses (Wang et al. 2002). MST1R is upregulated in many epithelial cancers where it is thought to play a role in the progression of these types of cancer (Kretschmann et al. 2010).
Literature References
PubMed ID
Title
Journal
Year
12472665
Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities
Chen, YQ
,
Wang, MH
,
Zhou, YQ
Scand. J. Immunol.
2002
20545605
The macrophage stimulating protein/Ron pathway as a potential therapeutic target to impede multiple mechanisms involved in breast cancer progression
Kretschmann, KL
,
Buys, SS
,
Eyob, H
,
Welm, AL
Curr Drug Targets
2010
Participants
Events
HPN heterodimer cleaves pro-MST1 to form MST1 dimer
(Homo sapiens)
MST1 binds MST1R
(Homo sapiens)
MST1 dimer:MST1R dimer binds MST1R dimer
(Homo sapiens)
MST1R autophosphorylates
(Homo sapiens)
Participates
as an event of
Signaling by Receptor Tyrosine Kinases (Homo sapiens)
Event Information
Go Biological Process
hepatocyte growth factor receptor signaling pathway (0048012)
Orthologous Events
Signaling by MST1 (Bos taurus)
Signaling by MST1 (Caenorhabditis elegans)
Signaling by MST1 (Canis familiaris)
Signaling by MST1 (Danio rerio)
Signaling by MST1 (Gallus gallus)
Signaling by MST1 (Mus musculus)
Signaling by MST1 (Rattus norvegicus)
Signaling by MST1 (Sus scrofa)
Signaling by MST1 (Xenopus tropicalis)
Authored
Jassal, B (2016-01-18)
Reviewed
D'Eustachio, P (2016-01-11)
Created
Jassal, B (2016-01-18)
© 2024
Reactome
Cite Us!
Cite Us!
Cite Us!
Warning!
Unable to extract citation. Please try again later.
Download As:
BibTeX
RIS
Text