A novel type I cytokine receptor is expressed on monocytes, signals proliferation, and activates STAT-3 and STAT-5.
Here we report the cloning of a novel type I cytokine receptor, gp130-like monocyte receptor (GLM-R), with homology to the interleukin-6 receptor signal transducing chain, gp130, and granulocyte colony-stimulating factor receptor. Human and murine GLM-R cDNAs encode open reading frames of 732 and 716 amino acids, respectively, and the corresponding genes are located in close proximity to gp130 genes on human chromosome 5 and mouse chromosome 13. GLM-R is specifically expressed on CD14-positive cells and is up-regulated more than 50-fold upon activation of those cells. To address the question of whether GLM-R is a signaling receptor, we constructed a chimeric molecule, consisting of the extracellular domain of human growth hormone (hGH) receptor, and the intracellular domain of GLM-R. When transfected into factor-dependent 32D cells, this chimeric molecule could signal for proliferation and activate signal transducer and activator of transcription (STAT)-3 and STAT-5 upon stimulation with hGH. Thus, GLM-R is a novel signaling receptor chain potentially involved in the development and function of monocytes and macrophages.
Ghilardi
Nico
N
Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
Li
Ji
J
Hongo
Jo-Anne
JA
Yi
Sothy
S
Gurney
Austin
A
de Sauvage
Frederic J
FJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008894:Milk Proteins; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C456339:cytokine receptor, GLM-R; D019382:Human Growth Hormone