Copyright ©The Author(s) 2021.
World J Gastroenterol. May 28, 2021; 27(20): 2507-2520
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2507
Figure 1
Figure 1 Mechanisms of RON activation and downstream signaling pathways. Classically, macrophage-stimulating protein (MSP) activates RON. In cancer, RON activation is induced by overexpression, splicing or truncation, and transactivation. The RON receptor consists of three regions including the extracellular domain, the transmembrane domain, as well as the intracellular domain. MSP binding to the extracellular domain leads to autophosphorylation of several tyrosine residues in the kinase activation loop or in the C-terminal tail, resulting in the activation of many biological activities, including increased proliferation/survival, motile-invasive activity, and chemoresistance. MSP: Macrophage-stimulating protein; SOS: Son of Sevenless; GRB2: Growth factor receptor-bound protein 2; CBL: Casitas B-lineage lymphoma; 14-3-3: Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein; PI-3K-AKT: Phosphatidylinositol-4,5-Bisphosphate 3 kinase- protein kinase B; HIF: Hypoxia-inducible factor; RAS-MAPK: RAS-mitogen-activated protein kinase; ERK: Extracellular regulated kinase; RSK: Ribosomal protein S6 kinase; mTOR: Mechanistic target of rapamycin.