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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 |
Published version: | http://dx.doi.org/10.1074/jbc.272.15.9877 |
Appears in Collections: | Aurora harvest Medicine publications |
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