Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/9561
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Type: Journal article
Title: The role of disulfide-linked dimerization in interleukin-3 receptor signaling and biological activity
Author: Le, F.
Stomski, F.
Woodcock, J.
Lopez, A.
Gonda, T.
Citation: Journal of Biological Chemistry, 2000; 275(7):5124-5130
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2000
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Fei Le, Frank Stomski, Joanna M. Woodcock, Angel F. Lopez and Thomas J. Gonda
Abstract: Cysteine residues 86 and 91 of the beta subunit of the human interleukin (hIL)-3 receptor (hbetac) participate in disulfide-linked receptor subunit heterodimerization. This linkage is essential for receptor tyrosine phosphorylation, since the Cys-86 --> Ala (Mc4) and Cys-91 --> Ala (Mc5) mutations abolished both events. Here, we used these mutants to examine whether disulfide-linked receptor dimerization affects the biological and biochemical activities of the IL-3 receptor. Murine T cells expressing hIL-3Ralpha and Mc4 or Mc5 did not proliferate in hIL-3, whereas cells expressing wild-type hbetac exhibited rapid proliferation. However, a small subpopulation of cells expressing each mutant could be selected for growth in IL-3, and these proliferated similarly to cells expressing wild-type hbetac, despite failing to undergo IL-3-stimulated hbetac tyrosine phosphorylation. The Mc4 and Mc5 mutations substantially reduced, but did not abrogate, IL-3-mediated anti-apoptotic activity in the unselected populations. Moreover, the mutations abolished IL-3-induced JAK2, STAT, and AKT activation in the unselected cells, whereas activation of these molecules in IL-3-selected cells was normal. In contrast, Mc4 and Mc5 showed a limited effect on activation of Erk1 and -2 in unselected cells. These data suggest that whereas disulfide-mediated cross-linking and hbetac tyrosine phosphorylation are normally important for receptor activation, alternative mechanisms can bypass these requirements.
Keywords: Cell Line; Animals; Humans; Mice; Disulfides; Cysteine; Protein-Serine-Threonine Kinases; Receptors, Interleukin-3; Proto-Oncogene Proteins; Transcription Factors; Signal Transduction; MAP Kinase Signaling System; Mutagenesis; Dimerization; Proto-Oncogene Proteins c-akt; Protein-Tyrosine Kinases; Janus Kinase 2
RMID: 0001001612
DOI: 10.1074/jbc.275.7.5124
Appears in Collections:Medicine publications

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