Premium
Expression and functional analysis of two isoforms of the human GM‐CSF receptor α chain in myeloid development and leukaemia
Author(s) -
Crosier Kathryn E.,
Hall Louanne R.,
Vitas Maria R.,
Crosier Philip S.
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.2653082.x
Subject(s) - biology , receptor , gene isoform , cell culture , haematopoiesis , myeloid , microbiology and biotechnology , common gamma chain , cell surface receptor , cellular differentiation , immunology , stem cell , interleukin 21 receptor , gene , genetics
The human granulocyte‐macrophage colony‐stimulating factor receptor (GM‐CSFR) α chain RNA is alternatively spliced to yield receptor isoforms. Two of these, α 1 and α 2 , differ in their cytoplasmic domains. Because the GM‐CSFR β chain (β c ) is shared with the receptors for interleukins 3 and 5 it is possible that the α 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 α 1 and α 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 α 1 or α 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 α 1 or α 2 receptor. These studies demonstrate that the α 1 and α 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.