Il15:Il15ra:p-Y-Il2rb:p-Y-Jak1:p-Y-Il2rg:p-Y-Jak3:p-Y-Shc1:Grb2:Gab2 phosphorylates Gab2

Stable Identifier
R-MMU-9007137
Type
Reaction [omitted]
Species
Mus musculus
Compartment
plasma membrane, cytosol, extracellular region
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Il15:Il15ra:p-Y-Il2rb:p-Y-Jak1:p-Y-Il2rg:p-Y-Jak3:p-Y-Shc1:Grb2:Gab2 phosphorylates Gab2
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).
Literature References
PubMed ID Title Journal Year
9660791 A new tyrosine-phosphorylated 97-kDa adaptor protein mediates interleukin-2-induced association of SHP-2 with p85-phosphatidylinositol 3-kinase in human T lymphocytes

Gesbert, F, Guenzi, C, Bertoglio, J

J. Biol. Chem. 1998
10849428 The docking molecule gab2 is induced by lymphocyte activation and is involved in signaling by interleukin-2 and interleukin-15 but not other common gamma chain-using cytokines

Gadina, M, Sudarshan, C, Visconti, R, Zhou, YJ, Gu, H, Neel, BG, O'Shea, JJ

J. Biol. Chem. 2000
19523893 How to Grb2 a Gab

Wöhrle, FU, Daly, RJ, Brummer, T

Structure 2009
Participants
Input
Output
Catalyst Activity

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]

Physical Entity
Il15:Il15ra:p-Y-Il2rb:p-Y-Il2rg:p-Y-Jak1:p-Y-Jak3:p-Y-Shc:Grb2:Gab2 [plasma membrane] (Mus musculus)
Activity
transmembrane receptor protein tyrosine kinase activity (GO:0004714)
Orthologous Events
IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3:p-Y-SHC1:GRB2:GAB2 phosphorylates GAB2 (Homo sapiens)
Authored
Duenas, C  (2017-08-07)
Reviewed
Patidar, M  (2017-08-07)
Created
Duenas, C  (2017-05-26)
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