Distinct regions of the human granulocyte-colony-stimulating factor receptor cytoplasmic domain are required for proliferation and gene induction.
Using two different cell systems, we show that the cytoplasmic domain of the granulocyte-colony-stimulating factor receptor (G-CSFR) may be composed of at least two functional regions. The first, within the membrane-proximal 57 amino acids, is absolutely required to deliver a proliferative signal. This region contains two sequence motifs conserved between members of the hematopoietin receptor family. The second functional region resides between amino acids 57 and 96. This region is required for the induction of acute-phase plasma protein gene expression when the G-CSFR is transfected into human hepatoma cell lines. The G-CSFR-transfected hepatoma cells respond to G-CSF by increasing the production of the same set of plasma proteins as stimulated by interleukin-6, suggesting that the two cytokines share a common signal transduction pathway.
Ziegler
S F
SF
Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101.
Bird
T A
TA
Morella
K K
KK
Mosley
B
B
Gearing
D P
DP
Baumann
H
H
D000209:Acute-Phase Proteins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D003593:Cytoplasm / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins