Conservation of the genomic structure and receptor-mediated signaling between human and rat IL-24.
IL-24/MDA-7 is a new member of the IL-10 family of cytokines, which signals through two heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2). Previously, we identified a rat gene named mob-5, which encodes a secreted protein that shares a high degree of homology with human IL-24. Expression of mob-5 and its putative cell surface receptors was shown to be upregulated by oncogenic ras. Here we show that not only do rat mob-5 and human IL-24 share a strikingly similar genomic structure but also that the rat MOB-5 protein can bind to and signal through the human IL-24 receptors. Like human IL-24, binding of the rat MOB-5 protein to the human IL-24 receptors leads to activation of the JAK/STAT pathway, which in turn supports receptor-dependent survival and proliferation of Ba/F3 cells. Furthermore, using human colon cancer cell lines with somatic knockout of either the mutant or the wild-type k-ras allele, we demonstrate that the human IL-24 receptors also are upregulated by oncogenic ras. Taken together, these results provide strong experimental evidence that MOB-5 is indeed the rat homolog of human IL-24.
Wang
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M
Department of Cancer Biology, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
Tan
Z
Z
Thomas
E K
EK
Liang
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P
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D040461:Gene Components; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D051381:Rats; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism; D000099180:Interleukin-24
D016207:Cytokines; D007378:Interleukins; D018123:Receptors, Interleukin; D018631:ras Proteins; D000099180:Interleukin-24; C413022:IL24 protein, rat; C492510:interleukin-20 receptor; C415369:interleukin-22 receptor