Identification of a variable region within the cytoplasmic tail of the IL-2 receptor beta chain that is required for growth signal transduction.
Abstract
Interleukin-2 (IL-2) regulates numerous biological events, including T lymphocyte proliferation. Interleukin-2 receptor (IL-2R)-mediated signaling is triggered by ligand-induced heterodimerization of the IL-2R beta and gamma c subunits, which results in the activation of signaling intermediates that are associated with either IL-2R beta or gamma c. Previous mutagenesis studies of the IL-2R beta cytoplasmic tail demonstrated that the partially conserved box 1 and box 2 motifs and specific tyrosine residues are critical for growth signaling. By deletion and alanine scanning mutagenesis, another set of residues that are critical for IL-2R-mediated signaling has now been identified. These residues lie within the divergent 35-amino acid "spacer" region separating box 1 and box 2. The role of this receptor subregion in early phases of IL-2R signaling was evaluated using BA/F3 stable cell lines expressing three functionally impaired mutants from this region. All three cell lines displayed substantially diminished growth responsiveness to IL-2. Receptor-mediated STAT factor activation, IL-2R beta phosphorylation, and Janus kinase activation were also markedly impaired. These findings indicate that this variable spacer region, which we ...Continue Reading
References
Signaling through the interleukin 2 receptor beta chain activates a STAT-5-like DNA-binding activity
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