Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/8914
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Type: Journal article
Title: The apoptosis-inducing granulocyte-macrophage colony-stimulating factor (GM-CSF) analog E21R functions through specific regions of the heterodimeric GM-CSF receptor, and requires interleukin-1 beta converting enzyme-like proteases.
Author: Iversen, P.
Hercus, T.
Zacharakis, B.
Woodcock, J.
Stomski, F.
Kumar, S.
Nelson, B.
Miyajima, A.
Lopez, A.
Citation: Journal of Biological Chemistry, 1997; 272(15):9877-9883
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Issue Date: 1997
ISSN: 0021-9258
1083-351X
Abstract: The granulocyte-macrophage colony-stimulating factor (GM-CSF) analog E21R induces apoptosis of hemopoietic cells. We examined the GM-CSF receptor subunit requirements and the signaling molecules involved. Using Jurkat T cells transfected with the GM-CSF receptor we found that both receptor subunits were necessary for E21R-induced apoptosis. Specifically, the 16 membrane-proximal residues of the alpha subunit were sufficient for apoptosis. This sequence could be replaced by the corresponding sequence from the interleukin-2 receptor common gamma subunit, identifying this as a conserved cytokine motif necessary for E21R-induced apoptosis. Cells expressing the alpha subunit and truncated betac mutants showed that the 96 membrane-proximal residues of betac were sufficient for apoptosis. E21R, in contrast to GM-CSF, did not alter tyrosine phosphorylation of betac, suggesting that receptor-associated tyrosine kinases were not activated. Consistent with this, E21R decreased the mitogen-activated protein kinase ERK (extracellular signal-regulated kinase). E21R-induced apoptosis was independent of Fas/APO-1 (CD95) and required interleukin-1beta-converting enzyme (ICE)-like proteases. In contrast, Bcl-2, which protects cells from growth factor deprivation-induced cell death, did not prevent this apoptosis. These findings demonstrate the GM-CSF receptor and ICE-like protease requirements for E21R-induced apoptosis.
Keywords: Hematopoietic Stem Cells
Jurkat Cells
Cytoplasm
Humans
Cysteine Endopeptidases
Caspase 1
Mitogen-Activated Protein Kinases
JNK Mitogen-Activated Protein Kinases
Amino Acid Chloromethyl Ketones
Granulocyte-Macrophage Colony-Stimulating Factor
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
Recombinant Proteins
Interleukin-1
Apoptosis
Down-Regulation
Phosphorylation
Calcium-Calmodulin-Dependent Protein Kinases
DOI: 10.1074/jbc.272.15.9877
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