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Identification of a novel ligand-receptor pair constitutively activated by ras oncogenes Zhang R; Tan Z; Liang PJ Biol Chem 2000[Aug]; 275 (32): 24436-43The Ras signaling pathway is thought to control the expression of a subset of yet to be defined genes that are crucial for cell growth and differentiation. Here we have identified by differential display a novel oncogenic Ras target, mob-5, encoding a 23-kDa cytokine-like secreted protein. Mob-5 expression could be induced by oncogenic Ha-ras and Ki-ras, but not by normal ras activation. Inhibitors of both Ha-Ras and mitogen-activated protein kinase kinase completely abolished the mob-5 expression in ras transformed cells, with concomitant loss of the transformation phenotype. Using an alkaline phosphatase-tagged Mob-5 as ligand, a putative Mob-5 receptor was identified on the cell surface of oncogenic ras transformed cells. Thus, the Mob-5/Mob-5 receptor may represent a novel putative autocrine loop coordinately activated by ras oncogenes.|*Cell Transformation, Neoplastic[MESH]|*Gene Expression Regulation[MESH]|*Genes, ras[MESH]|*Interleukins[MESH]|Amino Acid Sequence[MESH]|Animals[MESH]|Base Sequence[MESH]|Carrier Proteins/biosynthesis/chemistry/*genetics[MESH]|Cell Line[MESH]|Cytokines/biosynthesis/chemistry/*genetics[MESH]|Enzyme Inhibitors/pharmacology[MESH]|Flavonoids/pharmacology[MESH]|Genes, Tumor Suppressor[MESH]|Growth Substances/*genetics[MESH]|Humans[MESH]|Ligands[MESH]|Molecular Sequence Data[MESH]|Proto-Oncogene Proteins p21(ras)/genetics/*metabolism[MESH]|Rats[MESH]|Recombinant Fusion Proteins/biosynthesis[MESH]|Sequence Alignment[MESH]|Sequence Homology, Amino Acid[MESH] |
