DISTINCT TYROSINE RESIDUES WITHIN THE INTERLEUKIN-2 RECEPTOR-BETA CHAIN DRIVE SIGNAL-TRANSDUCTION SPECIFICITY, REDUNDANCY, AND DIVERSITY

Citation
Sl. Gaffen et al., DISTINCT TYROSINE RESIDUES WITHIN THE INTERLEUKIN-2 RECEPTOR-BETA CHAIN DRIVE SIGNAL-TRANSDUCTION SPECIFICITY, REDUNDANCY, AND DIVERSITY, The Journal of biological chemistry, 271(35), 1996, pp. 21381-21390
Citations number
53
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
271
Issue
35
Year of publication
1996
Pages
21381 - 21390
Database
ISI
SICI code
0021-9258(1996)271:35<21381:DTRWTI>2.0.ZU;2-Q
Abstract
To explore the basis for interleukin (IL)-2 receptor (IL-2R) signaling specificity, the roles of tyrosine-based sequences located within the cytoplasmic tails of the beta and gamma(c) chains were examined in th e murine helper T cell line HT-2, Activation of the Janus kinase/signa l transducer and activator of transcription (JAK/STAT) pathway, cellul ar proliferation, and the induction of various genes were monitored, A ll four of the cytoplasmic tyrosine residues as well as the distal por tion of the gamma(c) proved dispensable for the entire spectrum of IL- 2R signaling responses studied. Conversely, select tyrosine residues w ithin the beta chain were essential and differentially required for va rious signaling events, Specifically, activation of c-fos gene express ion was found to occur exclusively through the most membrane proximal tyrosine, Tyr-338, whereas proliferation and the activation of STAT-5 were induced either through Tyr-338 or through the two C-terminal tyro sine residues, Tyr-392 and Tyr-510, These tyrosine residues mediated t he induction of two different STAT-5 isoforms, which were found to for m heterodimers upon receptor activation, In contrast to the tyrosine d ependence of c-fos and STAT-5 induction, bcl-2 gene induction proceede d independently of all IL-2R beta tyrosine residues, Thus, the tyrosin e-based modules present within the IL-2R beta cytoplasmic tail play a critical role in IL-2R signaling, mediating specificity, redundancy, a nd multifunctionality.