Functional replacement of cytokine receptor extracellular domains by leucine zippers.

The Journal of Biological Chemistry
N PatelR A Kastelein

Abstract

Granulocyte-macrophage colony-stimulating factor receptor signals by a complex which includes the ligand and two different receptor subunits: a low affinity alpha receptor binding chain (granulocyte-macrophage colony-stimulating factor receptor alpha subunit (GM-Ralpha)) and a signal-transducing beta chain (GM-Rbeta). To investigate two unresolved issues in the initiation of signaling, the role of receptor extracellular domains and receptor stoichiometry, we replaced the mouse GM-Ralpha and GM-Rbeta extracellular domains with the leucine zipper domain of either the Fos or Jun molecule. We co-transfected combinations of chimeric receptors into Ba/F3 cells and found that both simple heterodimers of the GM-Ralpha and GM-Rbeta intracellular domains and homodimers of the GM-Rbeta intracellular domain signaled for proliferation. Surprisingly, homodimers of the GM-Ralpha intracellular domain also signaled for prevention of apoptosis in transfected cells. We similarly engineered dimers of the intracellular domain of the human interferon gamma receptor beta subunit and found that homodimers of the intracellular domain signaled for proliferation. When Fos peptide was added to Ba/F3 cells expressing the human interferon gamma receptor bet...Continue Reading

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Citations

Apr 12, 2001·European Journal of Immunology·L ZabeauJ Tavernier
Oct 29, 1998·Journal of Chromatography. B, Biomedical Sciences and Applications·H ChaoR S Hodges
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Stephane WongOwen N Witte
Apr 28, 2004·Cytokine & Growth Factor Reviews·Richard J D'AndreaThomas J Gonda
Feb 7, 2015·The Biochemical Journal·Michael J Waters, Andrew J Brooks
Nov 7, 2019·Cancers·Neele Schumacher, Stefan Rose-John

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis