Identification of a novel ligand-receptor pair constitutively activated by ras oncogenes.
The 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.
Zhang
R
R
Vanderbilt-Ingram Cancer Center, Department of Cell Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA.
Tan
Z
Z
Liang
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007378:Interleukins; D008024:Ligands; D008969:Molecular Sequence Data; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000099180:Interleukin-24
D002352:Carrier Proteins; D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006133:Growth Substances; D007378:Interleukins; D008024:Ligands; D016283:Proto-Oncogene Proteins p21(ras); D011993:Recombinant Fusion Proteins; D000099180:Interleukin-24; C413022:IL24 protein, rat; C501009:HRAS protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one