Grb2 associated binding protein 2 (Gab2) is phosphorylated in response to Interleukin-2 (Il2) and Interleukin-15 (Il15) stimulation. Its phosphorylation is greatly diminished by mutation of the site in the Interleukin-2 Receptor beta chain (Y338F) (Il2rb, Il2rβ) that recruits SHC transforming protein 1 (Shc1) (Gadina et al. 2000, Wöhrle et al. 2009, Gesbert et al. 1998, Brockdorff et al. 2001). The Il15 receptor complex consists mainly of Il15, Interleukin-15 receptor alpha subunit (Il15ra, Il15rα), IL2rb, which is associated with Jak1 and Interleukin receptor 2 gamma subunit, which is associated with Jak3 (Johnston et al. 1995). In this stage, it also includes a phosphorylated molecule of Shc1, a Grb2 and Gab2. This is a black box event because the kinase responsible for Gab2 phosphorylation has not been demonstrated. More in detail, human and mouse IL15 have 70.2% amino acid sequence similarity and exhibit similar trans-presentation mechanism, signal transduction machinery and biological activities. Similarly, human IL15 shows cross-reactivity with mouse cells and it was demonstrated that human and mouse IL15 showed similar responses in mouse models (Stoklasek et al. 2006) (Patidar et al. data not published).
Bertoglio, J, Guenzi, C, Gesbert, F
Neel, BG, Gadina, M, Gu, H, Sudarshan, C, Zhou, YJ, Visconti, R, O'Shea, JJ
Wöhrle, FU, Brummer, T, Daly, RJ
transmembrane receptor protein tyrosine kinase activity of Il15:Il15ra:p-Y-Il2rb:p-Y-Il2rg:p-Y-Jak1:p-Y-Jak3:p-Y-Shc:Grb2:Gab2 [plasma membrane]
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