Structure of the gene encoding the α subunit of the human granulocyte- macrophage colony stimulating factor receptor. Implications for the evolution of the cytokine receptor superfamily

Y. Nakagawa, H. Kosugi, A. Miyajima, K. I. Arai, T. Yokota

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The receptor for granulocyte-macrophage colony-stimulating factor (GM- CSF) is composed of at least two subunits, α and β. In addition to the conserved cysteine residues and a 'WSxWS' motif, the extracellular segments of both subunits have domains that are structurally related to a fibronectin type III domain. This structure is conserved in all members of the cytokine receptor superfamily. We isolated and characterized genomic DNA clones containing the entire coding sequences of the α subunit of the human GM-CSF receptor (hGMRα). The gene spans approximately 44 kilobases and has 13 exons. The major transcription initiation site was determined to be 195 base pairs upstream of the translation initiation site. The putative promoter region lacks a typical TATA motif and an Sp1 binding site, but contains a purine-rich stretch about 30 base pairs upstream of the transcription initiation site. This stretch is also found in the human interleukin 2 receptor γ subunit and granulocyte colony-stimulating factor receptor genes. We compared the exon-intron organization of the hGMRα gene with other members of the cytokine receptor superfamily and found the genomic organizations to be remarkably well conserved. On the basis of these observations, we propose a model for evolution of this gene family.

Original languageEnglish (US)
Pages (from-to)10905-10912
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number14
StatePublished - Jan 1 1994

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