Oncogenic signaling pathways activated by RON receptor tyrosine kinase.
RON (Receptuer d'Origine Nantaise) is a member of the MET receptor tyrosine kinase family. RON is expressed in various cell types including macrophages, epithelial and hematopoietic cells. Its ligand, macrophage stimulating protein (MSP, also known as hepatocyte growth factor-like protein), is a multifunctional factor regulating cell growth and survival, adhesion and motility, cytokine production and phagocytosis. Accumulated data indicate that in addition to the regulation of normal cell functions, RON can be involved in cancer development and progression: (i). RON is overexpressed and constitutively active in some primary tumors and tumor cell lines; (ii). experimental mutations of RON cause oncogenic cell transformation, and (iii). RON mediates susceptibility to Friend-virus-induced erythroleukemia in mice. Constitutive activation of intracellular signaling pathways such as the PI-3 kinase/AKT, beta-catenin, MAPK and JNK pathways may underlie the molecular mechanism of RON-mediated oncogenic cell transformation. The present review describes RON-activated signaling pathways, which may play an important role in tumor formation and metastasis.
Danilkovitch-Miagkova
Alla
A
Department of Immunochemistry, PPD Development, 2244 Dabney Road, Richmond, VA 23230, USA. Alla.Danilkovitch@richmond.ppdi.com
D000818:Animals; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D011494:Protein Kinases; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases