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Updated: Jul 28, 2026

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Anti-apoptotic action of macrophage stimulating protein (MSP)
A Danilkovitch-Miagkova1, E J Leonard
1Section of Immunopathology, Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland 21702, USA. danilkovitch@mail.ncifcrf.gov
Abstract:
MSP is a serum protein belonging to the plasminogen-related kringle domain protein family. In addition to macrophages, epithelial cells are also MSP targets. MSP is a multifunctional factor regulating cell adhesion and motility, growth and survival. MSP mediates its biological activities by activating a transmembrane receptor tyrosine kinase called RON in humans or SKT in mice. MSP can protect epithelial cells from apoptosis by activating two independent signals in the PI3-K/AKT or the MAPK pathway. The MAPK pathway mediates the MSP antiapoptotic effect only if additional signaling pathways are activated through adhesion. This indicates that MSP receptors and integrins, the receptors mediating cell-matrix-dependent adhesion, can collaborate in promotion of cell survival. This adhesion-dependent pathway, which is essential for the MAPK-mediated anti-apoptotic effect, remains to be identified. A hypothesis that Stat3 might represent a key component of the adhesion-induced anti-apoptotic pathway is presented in this review.
Insights
Macrophage-stimulating protein (MSP) protects epithelial cells from apoptosis by activating PI3-K/AKT or MAPK pathways. Adhesion-dependent pathways involving MSP receptors and integrins are crucial for MSP
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- The serum protein Macrophage-Stimulating Protein (MSP) is a multifunctional factor regulating cell adhesion, motility, growth, and survival.
- MSP targets include macrophages and epithelial cells, mediating its effects via the receptor tyrosine kinase RON (human) or SKT (mouse).
Purpose of the Study:
- To review the mechanisms by which MSP protects epithelial cells from apoptosis.
- To explore the collaborative roles of MSP receptors and integrins in cell survival signaling.
- To hypothesize potential components of adhesion-dependent anti-apoptotic pathways activated by MSP.
Main Methods:
- Review of existing literature on MSP signaling pathways.
- Analysis of MSP's interaction with receptor tyrosine kinases (RON/SKT) and integrins.
- Examination of downstream signaling cascades including PI3-K/AKT and MAPK pathways.
Main Results:
- MSP activates either the PI3-K/AKT pathway or the MAPK pathway to confer anti-apoptotic effects on epithelial cells.
- The anti-apoptotic function of the MAPK pathway is dependent on additional signaling activated through cell adhesion.
- MSP receptors and integrins cooperate to promote cell survival, suggesting a complex interplay in anti-apoptotic signaling.
Conclusions:
- MSP plays a significant role in epithelial cell survival through distinct signaling pathways.
- Adhesion-dependent signaling is critical for the full anti-apoptotic effect mediated by MSP via the MAPK pathway.
- Signal transducer and activator of transcription 3 (Stat3) is hypothesized as a key component in the adhesion-induced anti-apoptotic pathway activated by MSP.
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