RON Receptor

Danilkovitch-Miagkova A., Leonard E.J.

RON (Receptuer d’Origine Nantaise) is a transmembrane receptor tyrosine kinase (RTK) that belongs to the MET receptor tyrosine kinase protein family. RON is expressed in various cell types including macrophages, osteoclasts, epithelial cells, and hematopoietic cells. The RON ligand is macrophage-stimulating protein (MSP). MSP is a member of the kringle-domain plasminogen-related protein family; its sequence is similar to that of the MET ligand hepatocyte growth factor (HGF). MSP binding to RON activates a number of intracellular signaling pathways that mediate MSP biological activities, including its effects on adhesion and motility, growth, differentiation, and survival. MSP /RON-induced cellular responses suggest an important role oi RON in the regulation of normal cell functions and possible involvement in various pathological conditions. Addition of MSP to macrophages expressing RON induces shape changes, chemotaxis. macropino-cytosis. and phagocytosis. RON activation inhibits generation of nitric oxide (NO) by endotoxin and thus suppresses endotoxin lethality. RON promotes adhesion and motility, growth and survival of epithelial cells. Normal RON is overexpressed by a variety of tumors and transfection of mutated forms oi RON results in oncogenic transformation. Lethality of RON knockout mice reflects the importance of RON in embryonal development. This review provides a complete RON reference guide showing key points for future directions in RON investigations.