Differentiation-linked changes in tyrosine phosphorylation, functional activity, and gene expression downstream from the granulocyte- macrophage colony-stimulating factor receptor

Content Provider	Scilit
Author	Roberts, Pj Khwaja, A. Lie, Ak Bybee, A. Yong, K. Thomas, Ns Linch, Dc
Copyright Year	1994
Description	The HL-60 model of myeloid maturation was used to test whether changes in signaling from the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor accompany maturation-related changes in cellular responses to GM-CSF. Receptor expression, tyrosine phosphorylation, functional activity, and c-fos gene expression were measured. Functional GM-CSF receptors were present throughout differentiation as both uninduced and dimethyl sulfoxide (DMSO)-induced HL-60 cells responded to GM-CSF, albeit in different ways. Uninduced promyelocytes proliferated in response to GM-CSF, whereas DMSO-induced cells lost the capacity to proliferate but did respond with increased expression of beta 2-integrins, enhanced respiratory burst activity, and metabolism of arachidonic acid. GM-CSF-stimulated upregulation of c-fos mRNA expression was not detected in immature cells but developed after 2 to 4 days with DMSO in line with a marked increase in responsiveness to stimulation with phorbol ester, showing that increased expression of c- fos is predominantly a feature of mature phagocytes. GM-CSF stimulated the tyrosine phosphorylation of a broadly similar range of proteins in both uninduced and DMSO-treated HL-60 cells, but protein bands were more heavily phosphorylated in DMSO-induced cells. Phosphorylation was rapid in onset and very transient in immature cells. Phosphorylation of several proteins, in particular a 130-kD band, was more sustained in DMSO-induced cells. These differences in signaling were not because of numerical differences in receptors, because reduction of GM-CSF concentration to trigger equivalent numbers of high-affinity receptors delayed the onset of phosphorylation in DMSO-induced cells. We conclude that there are maturation-related changes in signaling downstream from the GM-CSF receptor.
Related Links	https://ashpublications.org/blood/article-pdf/84/4/1064/231152/1064.pdf
Ending Page	1073
Page Count	10
Starting Page	1064
DOI	10.1182/blood.v84.4.1064.bloodjournal8441064
Journal	Blood
Issue Number	4
Volume Number	84
Language	English
Publisher	American Society of Hematology
Publisher Date	1994-08-15
Access Restriction	Open
Subject Keyword	Biochemistry and Molecular Biology Differentiation Gene Expression Phosphorylation Proteins Functional Downstream Csf Receptors Maturation Related Changes Journal: Blood (Vol- 77, Issue- 4)
Content Type	Text
Resource Type	Article