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Updated: Jul 31, 2025

Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
Published on: April 18, 2025
A network map of macrophage-stimulating protein (MSP) signaling
Diya Sanjeev1, Shobha Dagamajalu2, Vineetha Shaji3
1Centre for Integrative OmicsData Science (CIODS), Yenepoya (Deemed to be University), Derlakatte, Mangalore, Karnataka, 575018, India.
Abstract:
Macrophage-stimulating protein (MSP), a serum-derived growth factor belonging to the plasminogen-related kringle domain family, is mainly produced by the liver and released into the blood. MSP is the only known ligand for RON ("Recepteur d'Origine Nantais", also known as MST1R), which is a member of the receptor tyrosine kinase (RTK) family. MSP is associated with many pathological conditions, including cancer, inflammation, and fibrosis. Activation of the MSP/RON system regulates main downstream signaling pathways, including phosphatidylinositol 3-kinase/ AKT serine/threonine kinase/ (PI3-K/AKT), mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK) & Focal adhesion kinase (FAK). These pathways are mainly involved in cell proliferation, survival, migration, invasion, angiogenesis & chemoresistance. In this work, we created a pathway resource of signaling events mediated by MSP/RON considering its contribution to diseases. We provide an integrated pathway reaction map of MSP/RON that is composed of 113 proteins and 26 reactions based on the curation of data from the published literature. The consolidated pathway map of MSP/RON mediated signaling events contains seven molecular associations, 44 enzyme catalysis, 24 activation/inhibition, six translocation events, 38 gene regulation events, and forty-two protein expression events. The MSP/RON signaling pathway map can be freely accessible through the WikiPathways Database URL: https://classic.wikipathways.org/index.php/Pathway:WP5353 .
Insights
Macrophage-stimulating protein (MSP) and its receptor RON are crucial in cell signaling, impacting diseases like cancer. This study maps the MSP/RON pathway, detailing its molecular interactions and disease relevance.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Macrophage-stimulating protein (MSP) is a serum growth factor produced by the liver.
- MSP is the sole ligand for the receptor tyrosine kinase (RTK) RON (MST1R).
- The MSP/RON system is implicated in various pathologies, including cancer, inflammation, and fibrosis.
Purpose of the Study:
- To create a comprehensive pathway resource for MSP/RON signaling.
- To integrate signaling events mediated by MSP/RON, considering their role in disease.
Main Methods:
- Curated data from published literature.
- Developed an integrated pathway reaction map.
- Detailed molecular associations, enzyme catalysis, activation/inhibition, translocation, gene regulation, and protein expression events.
Main Results:
- Constructed a pathway map of MSP/RON signaling involving 113 proteins and 26 reactions.
- The map includes seven molecular associations, 44 enzyme catalysis events, 24 activation/inhibition events, six translocation events, 38 gene regulation events, and 42 protein expression events.
- The MSP/RON signaling pathway map is accessible via WikiPathways.
Conclusions:
- The MSP/RON signaling pathway is a key regulator of cellular processes like proliferation, survival, migration, invasion, angiogenesis, and chemoresistance.
- This pathway resource provides valuable insights into MSP/RON's contribution to various diseases.
- The detailed map facilitates further research into MSP/RON-mediated signaling and therapeutic strategies.

