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Anti-apoptotic action of macrophage stimulating protein (MSP)

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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 anti-apoptotic 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.

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Authors and Affiliations

  1. Section of Immunopathology, Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland, 21702, USA

    A. Danilkovitch-Miagkova

  2. Section of Immunopathology, Laboratory of Immunobiology, National Cancer Institute, Frederick, Maryland, 21702, USA

    E. J. Leonard

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  1. A. Danilkovitch-Miagkova
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Danilkovitch-Miagkova, A., Leonard, E.J. Anti-apoptotic action of macrophage stimulating protein (MSP). Apoptosis 6, 183–190 (2001). https://doi.org/10.1023/A:1011384609811

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