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Signaling by MST1

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-8852405

PubChem

R-HSA-8852405

Description

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).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 5** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O43278	Kunitz-type protease inhibitor 1	HAI1 SPINT1 UNQ223/PRO256	view
O43291	Kunitz-type protease inhibitor 2	HAI2 KOP SPINT2	view
P05981	Serine protease hepsin	HPN TMPRSS1	view
P26927	Hepatocyte growth factor-like protein	D3F15S2 DNF15S2 HGFL MST1 hCG_2001992	view
Q04912	Macrophage-stimulating protein receptor	MST1R PTK8 RON	view

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