rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils.
Stimulation of neutrophils with granulocyte-colony stimulating factor (G-CSF) results in an enhanced respiratory burst, prolonged survival, and increased tumor cell killing. The effects of G-CSF are mediated by binding to specific, high affinity receptors. G-CSF receptors lack intrinsic tyrosine kinase activity, but activation of the receptor results in the rapid induction of tyrosine kinase activity. Antiphosphotyrosine immunoblots of whole cell lysates prepared from neutrophils show that the G-CSF rapidly induces prominent tyrosine phosphorylation of a protein of a relative molecular mass of 80 kDa. Using monospecific antibodies, the 80-kDa tyrosine-phosphorylated protein has been shown to be p80c-rel, a proto-oncogene belonging to a family of transcriptional regulators which include NF-kB. The induction of tyrosine phosphorylation of p80c-rel was unique to G-CSF in that granulocyte-macrophage colony stimulating factor which also stimulates neutrophils and induces tyrosine phosphorylation does not result in tyrosine phosphorylation of p80c-rel. The consequences of p80c-rel tyrosine phosphorylation are not yet known; however, tyrosine-phosphorylated p80c-rel is capable of binding to DNA, and G-CSF stimulation results in an increase in the amount of p80c-rel which binds to DNA. These results demonstrate that one of the first biochemical events which occurs in neutrophils following G-CSF stimulation, activation of a tyrosine kinase, leads directly to the tyrosine phosphorylation of p80c-rel. Thus, the tyrosine kinase activated by G-CSF appears to directly transduce a signal to a protein which functions as a transcriptional regulator.
Druker
B J
BJ
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Neumann
M
M
Okuda
K
K
Franza
B R
BR
Griffin
J D
JD
D000328:Adult; D002846:Chromatography, Affinity; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000097:blood / Q000302:isolation & purification; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000097:blood*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000302:isolation & purification; D020569:Proto-Oncogene Proteins c-rel; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
C000715470:MAS1 protein, human; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D011994:Recombinant Proteins; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D019000:Phosphotyrosine; D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases