Structure of the gene encoding the alpha subunit of the human granulocyte-macrophage colony stimulating factor receptor. Implications for the evolution of the cytokine receptor superfamily.
The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of at least two subunits, alpha and beta. 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 alpha subunit of the human GM-CSF receptor (hGMR alpha). 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 gamma subunit and granulocyte colony-stimulating factor receptor genes. We compared the exon-intron organization of the hGMR alpha 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.
Nakagawa
Y
Y
Department of Molecular and Developmental Biology, University of Tokyo, Japan.
Kosugi
H
H
Miyajima
A
A
Arai
K
K
Yokota
T
T
D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D004247:DNA; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D018121:Receptors, Cytokine / Q000235:genetics*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D016385:TATA Box; D014158:Transcription, Genetic
D018121:Receptors, Cytokine; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016329:Sp1 Transcription Factor; D004247:DNA