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Conservation of the genomic structure and receptor-mediated signaling between human and rat IL-24

Genes & Immunity volume 5, pages 363–370 (2004)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr S Kotenko for the gift of the IL-24 receptor expression vecters, Dr R Coffey (Vanderbilt University) for providing DLD-1, DKO-1 and DKS-8 cell lines. We are grateful for RS Jackson II and Dr S Stein for their critical comments on the manuscript. This work was supported in part by NIH grant CA 74067.

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  1. Department of Cancer Biology, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA

    M Wang, Z Tan, E K Thomas & P Liang

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Correspondence to P Liang.

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Wang, M., Tan, Z., Thomas, E. et al. Conservation of the genomic structure and receptor-mediated signaling between human and rat IL-24. Genes Immun 5, 363–370 (2004). https://doi.org/10.1038/sj.gene.6364101

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