Activation of the interleukin 2 receptor: a possible role for tyrosine phosphatases

Abstract

Engagement of interleukin-2 (IL-2) mediates the heterodimeridation of the common beta chain (β c) and common gamma chain (γ c) of the IL-2 receptor (IL-2R). This is sufficient and necessary for receptor activation and signal transduction. It is generally held that the IL-2R is activated by the trans-activity of the protein tyrosine kinases (PTKs) Jak1 and Jak3 associated with β c and γ c respectively. Transduction of proliferative signals requires Jak3 activity. A Jak3 independent signalling pathway involving p56 lck , generating anti-apoptotic signals, can be observed and requires the PROX domain of γ c. p56 lck can be activated by dephosphorylation of an inhibitory carboxyl terminal phosphorylated tyrosine residue (Y505). We propose that this is mediated by a PROX domain associated protein tyrosine phosphatase (PTP). Activation of p56 lck alone is insufficient for transduction of proliferative signals and thus works in concert with Jak3 mediated receptor activation. This indicates that both γ c domains are vital for signal transduction.