, Volume 6, Issue 3, pp 183–190

Anti-apoptotic action of macrophage stimulating protein (MSP)

  • A. Danilkovitch-Miagkova
  • E. J. Leonard


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.

adhesion apoptosis epithelial cells MSP signaling 


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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • A. Danilkovitch-Miagkova
    • 1
  • E. J. Leonard
    • 2
  1. 1.Section of Immunopathology, Laboratory of ImmunobiologyNational Cancer Institute, FrederickUSA
  2. 2.Section of Immunopathology, Laboratory of ImmunobiologyNational Cancer Institute, FrederickUSA

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