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
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.