Anti-apoptotic action of macrophage stimulating protein (MSP)

MSP is a serum protein belonging to the plasminogen-related kringle domain protein family. In addition to macrophages, epithelial cells are also MSP t argets. MSP is a multifunctional factor regulating cell adhesion and motili ty, growth and survival. MSP mediates its biological activities by activati ng a transmembrane receptor tyrosine kinase called RON in humans or SKT in mice. MSP can protect epithelial cells from apoptosis by activating two ind ependent signals in the PI3-K/AKT or the MAPK pathway. The MAPK pathway med iates the MSP anti-apoptotic effect only if additional signaling pathways a re activated through adhesion. This indicates that MSP receptors and integr ins, the receptors mediating cell-matrix-dependent adhesion, can collaborat e in promotion of cell survival. This adhesion-dependent pathway, which is essential for the MAPK-mediated anti-apoptotic effect, remains to be identi fied. A hypothesis that Stat3 might represent a key component of the adhesi on-induced anti-apoptotic pathway is presented in this review.