Tyrosine residues of the granulocyte colony-stimulating factor transmit proliferation and differentiation signals in murine bone marrow cells

Arkbarzadeh, Shiva, Ward, Alister, McPhee, Dora O., Alexander, Warren S., Lieschke, Graham J. and Layton, Judith E. 2002, Tyrosine residues of the granulocyte colony-stimulating factor transmit proliferation and differentiation signals in murine bone marrow cells, Blood, vol. 99, no. 3, pp. 879-887.

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Title Tyrosine residues of the granulocyte colony-stimulating factor transmit proliferation and differentiation signals in murine bone marrow cells
Author(s) Arkbarzadeh, Shiva
Ward, Alister
McPhee, Dora O.
Alexander, Warren S.
Lieschke, Graham J.
Layton, Judith E.
Journal name Blood
Volume number 99
Issue number 3
Start page 879
End page 887
Publisher American Society of Hematology
Place of publication Washington D.C.
Publication date 2002-02
ISSN 0006-4971
1528-0020
Keyword(s) hemostasis
Summary Granulocyte colony-stimulating factor (G-CSF) is the major regulator of granulopoiesis and acts through binding to its specific receptor (G-CSF-R) on neutrophilic granulocytes. Previous studies of signaling from the 4 G-CSF-R cytoplasmic tyrosine residues used model cell lines that may have idiosyncratic, nonphysiological responses. This study aimed to identify specific signals transmitted by the receptor tyrosine residues in primary myeloid cells. To bypass the presence of endogenous G-CSF-R, a chimeric receptor containing the extracellular domain of the epidermal growth factor receptor in place of the entire extracellular domain of the G-CSF-R was used. A series of chimeric receptors containing tyrosine mutations to phenylalanine, either individually or collectively, was constructed and expressed in primary bone marrow cells from G-CSF-deficient mice. Proliferation and differentiation responses of receptor-expressing bone marrow cells stimulated by epidermal growth factor were measured. An increased 50% effective concentration to stimulus of the receptor Ynull mutant indicated that specific signals from tyrosine residues were required for cell proliferation, particularly at low concentrations of stimulus. Impaired responses by mutant receptors implicated G-CSF-R Y764 in cell proliferation and Y729 in granulocyte differentiation signaling. In addition, different sensitivities to ligand stimulation between mutant receptors indicated that G-CSF-R Y744 and possibly Y729 have an inhibitory role in cell proliferation. STAT activation was not affected by tyrosine mutations, whereas ERK activation appeared to depend, at least in part, on Y764. These observations have suggested novel roles for the G-CSF-R tyrosine residues in primary cells that were not observed previously in studies in cell lines.
Language eng
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2002, American Society of Hematology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006559

Document type: Journal Article
Collection: School of Medicine
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