rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils

Brian Druker, Manfred Neumann, Keiko Okuda, B. Robert Franza, James D. Griffin

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 p80(c-rel), a proto-oncogene belonging to a family of transcriptional regulators which include NF-kB. The induction of tyrosine phosphorylation of p80(c-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 p80(c-rel). The consequences of p80(c-rel) tyrosine phosphorylation are not yet known; however, tyrosine-phosphorylated p80(c- rel) is capable of binding to DNA, and G-CSF stimulation results in an increase in the amount of p80(c-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 p80(c-rel). Thus, the tyrosine kinase activated by G-CSF appears to directly transduce a signal to a protein which functions as a transcriptional regulator.

Original languageEnglish (US)
Pages (from-to)5387-5390
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number7
StatePublished - Feb 18 1994

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Granulocyte Colony-Stimulating Factor
Phosphorylation
Tyrosine
Neutrophils
Protein-Tyrosine Kinases
rel Genes
Granulocyte Colony-Stimulating Factor Receptors
Chemical activation
Proteins
Respiratory Burst
NF-kappa B
DNA
Molecular mass
Granulocyte-Macrophage Colony-Stimulating Factor
Tumors
Cells
Survival
Antibodies

ASJC Scopus subject areas

  • Biochemistry

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rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils. / Druker, Brian; Neumann, Manfred; Okuda, Keiko; Robert Franza, B.; Griffin, James D.

In: Journal of Biological Chemistry, Vol. 269, No. 7, 18.02.1994, p. 5387-5390.

Research output: Contribution to journalArticle

Druker, Brian ; Neumann, Manfred ; Okuda, Keiko ; Robert Franza, B. ; Griffin, James D. / rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 7. pp. 5387-5390.
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abstract = "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 p80(c-rel), a proto-oncogene belonging to a family of transcriptional regulators which include NF-kB. The induction of tyrosine phosphorylation of p80(c-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 p80(c-rel). The consequences of p80(c-rel) tyrosine phosphorylation are not yet known; however, tyrosine-phosphorylated p80(c- rel) is capable of binding to DNA, and G-CSF stimulation results in an increase in the amount of p80(c-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 p80(c-rel). Thus, the tyrosine kinase activated by G-CSF appears to directly transduce a signal to a protein which functions as a transcriptional regulator.",
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