Activation of the interleukin 2 receptor: a possible role for tyrosine phosphatases.
Engagement of interleukin-2 (IL-2) mediates the heterodimeridation of the common beta chain (beta(c)) and common gamma chain (gamma(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 beta(c) and gamma(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 gamma(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 gamma(c) domains are vital for signal transduction.
Ellery
J M
JM
Department of Biosciences University of Kent at Canterbury, Canterbury, United Kingdom.
Kempshall
S J
SJ
Nicholls
P J
PJ
D000818:Animals; D019281:Dimerization; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; C507905:Jak1 protein, mouse; C507935:Jak3 protein, mouse; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017027:Protein Tyrosine Phosphatases