J Immunol 1998,
PMID: 9794391
Lord, J D; McIntosh, B C; Greenberg, P D; Nelson, B H
IL-2, the principal mitogenic factor for activated T cells, delivers a proliferative signal through ligation of the heterotrimeric IL-2R. This proliferative signal is critically dependent upon cytoplasmic tyrosines on the beta-chain of this receptor (IL-2Rbeta) becoming phosphorylated in response to ligand. We found that at least one of these tyrosines (Y338) also mediates cell survival and induction of bcl-2, bcl-x, and c-myc in the murine T cell line CTLL-2. Since the adapter molecule Shc binds to phosphorylated Y338, the specific contribution of Shc to these events was evaluated. An IL-2Rbeta/Shc fusion protein, in which Shc was covalently tethered to a truncated version of IL-2Rbeta lacking all cytoplasmic tyrosines, revealed a robust proliferative signal mediated through Shc. This Shc-mediated signal induced expression of c-myc as well as the antiapoptotic genes bcl-2 and bcl-x with normal magnitude and kinetics. Nonetheless, signals from this fusion protein failed to sustain the long-term viability of CTLL-2 cells. Thus, induction of bcl family genes and delivery of a competent proliferative signal are not sufficient to promote cell survival and mediate the antiapoptotic effects associated with a complete IL-2 signal.
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Text Mining Data
bcl-x → IL-2: "
The
IL-2 receptor
promotes proliferation, bcl-2 and
bcl-x induction, but not cell viability through the adapter molecule Shc
"
Shc → bcl-x: "
This Shc mediated signal induced expression of c-myc as well as the antiapoptotic genes bcl-2 and bcl-x with normal magnitude and kinetics
"
Manually curated Databases
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NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1)
→
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3-SHC1)
→
SHC (SHC1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database IL2-mediated signaling events:
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3 complex (IL2RA-IL2RB-IL2RG-IL2-JAK1-LCK-JAK3)
→
SHC (SHC1)
(modification, collaborate)
Evidence: mutant phenotype, assay, physical interaction, other species
In total, 36 gene pairs are associated to this article in curated databases