Expression and functional analysis of two isoforms of the human GM-CSF receptor alpha chain in myeloid development and leukaemia.
The human granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain RNA is alternatively spliced to yield receptor isoforms. Two of these, alpha 1 and alpha 2, differ in their cytoplasmic domains. Because the GM-CSFR beta chain (beta c) is shared with the receptors for interleukins 3 and 5 it is possible that the alpha chain confers specificity on the GM-CSF response and that the different isoforms might refine this response further. Studies have been directed at determination of the respective biological roles of the alpha 1 and alpha 2 isoforms. Expression of the isoforms was examined by RNase protection analysis in normal granulocytes and a variety of cell lines of haemopoietic origin, at different stages of differentiation and activation. Expression was also analysed in cells from patients with a variety of leukaemic subtypes. Results demonstrated that the relative abundance of the isoforms was similar in all cell populations examined. The human GM-CSFR alpha 1 or alpha 2 receptors were independently expressed in the murine factor-dependent cell line FDC-P1, so that the properties of the receptors could be compared. Cell lines that expressed either receptor could be converted to growth in response to human GM-CSF and assumed a more differentiated phenotype when compared with the parental cell line. However, the morphology, expression of cell surface antigens and dose-growth response characteristics did not differ significantly between cells that expressed either the alpha 1 or alpha 2 receptor. These studies demonstrate that the alpha 1 and alpha 2 subunits of the GM-CSF receptor are co-ordinately regulated in both normal and malignant haemopoiesis. Furthermore, each receptor is able to deliver both proliferative and differentiative signals to myeloid cells.
Crosier
K E
KE
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
Hall
L R
LR
Vitas
M R
MR
Crosier
P S
PS
D000954:Antigens, Surface / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D007951:Leukemia, Myeloid / Q000473:pathology*; D008854:Microscopy, Electron; D009000:Monocytes / Q000473:pathology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000473:pathology; D012313:RNA / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D012313:RNA