Transcriptional activation of egr-1 by granulocyte-macrophage colony-stimulating factor but not interleukin 3 requires phosphorylation of cAMP response element-binding protein (CREB) on serine 133.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) stimulate the proliferation and maturation of myeloid progenitor cells following interaction with heterodimeric receptors that share a common beta subunit required for signal transduction. Our previous studies have demonstrated that GM-CSF and IL-3 activate signaling pathways which converge upon a cAMP response element-binding protein (CREB)-binding site of the human immediate early response gene (early growth response gene-1, egr-1) promoter. Using electromobility supershift assays and antibodies directed against CREB phosphorylated on serine 133, we show that CREB is phosphorylated on serine 133 in response to GM-CSF or IL-3 stimulation. We demonstrate that phosphorylation of CREB on serine 133 substantially contributes to transcriptional activation of egr-1 in response to GM-CSF but not IL-3. These studies suggest that phosphorylation of CREB may play different roles during signal transduction, resulting in unique and overlapping biological functions in myeloid cells.
Lee
H J
HJ
Gwynne Hazen Cherry Memorial Laboratories, Department of Pediatrics, UCLA School of Medicine 90095-1752, USA.
Mignacca
R C
RC
Sakamoto
K M
KM
D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells; D006801:Humans; D017874:Immediate-Early Proteins; D015151:Immunoblotting; D007377:Interleukin-3 / Q000494:pharmacology*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000096:biosynthesis; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis* / Q000235:genetics; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D007377:Interleukin-3; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D012694:Serine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor