Preferred Label : IL2RB Pathway;
NCIt related terms : IL-2 Receptor Beta Chain in T cell Activation;
Alternative definition : BIOCARTA: The IL-2 receptor is a key component of immune signaling and is required
for the activation, proliferation, and survival of T cells. This receptor is composed
of three polypeptide chains, the alpha, beta, and gamma chains. The IL-2 receptor
gamma chain is a common component for several other cytokine receptors, including
IL-4, IL-7, IL-9 and IL-15. The IL-2 receptor beta chain is essential for IL-2 signaling
and is also a component of the IL-15 receptor complex. The polypeptides of the IL-2
receptor do not themselves have intrinsic catalytic activity, but interact with cytoplasmic
signaling proteins to transduce signals. Different regions of the cytoplasmic domain
of the IL-2 receptor beta chain interact and couple with distinct signaling pathways
and cellular responses. JAK1 associates with the beta chain and JAK3 with the gamma
chain. Binding of IL-2 induces heterodimerization of receptor subunits, and activation
of JAK kinase activity. Tyrosine residues in the beta chain cytoplasmic domain are
phosphorylated during activation, recruiting other factors to the phosphorylated tyrosine
residues through src homology 2 (SH2) domains. The adaptor protein Shc binds to phosphorylated
tyrosine 338 of the beta chain. When bound, Shc is phosphorylated and couples through
Grb2 and Sos-1 to activate Ras and stimulate T cell proliferation. Another key proliferative
pathway activated by IL-2 is phosphorylation of STAT-5 by JAK kinases. STAT-5 is recruited
to IL-2 beta phosphorylated tyrosines at multiple positions, including Y338, Y392
and Y510. Once phosphorylated, STAT-5 enters the nucleus to regulate the transcription
of several genes, some proliferative, such as cyclin genes, and others that are involved
in T cell immune function such as cytokine genes. The suppressors of cytokine activation,
SOCS-3 and SOCS-1, oppose phosphorylation and activation of STAT-5 and JAK1 caused
by IL-2. PI3 kinase is another protein recruited to IL-2 receptor beta chain tyrosines
when phosphorylated. Activation of PI3 Kinase also contributes to the proliferative
activity of IL-2 in T cells. The role of other tyrosines in the IL-2 receptor beta
chain, Y355, Y358 and Y361, is not yet clear, but may be involved in signaling by
the protein kinase p56lck. In addition to stimulating T cell activation and proliferation,
IL-2 activation blocks T cell apoptosis through multiple pathways. Among the genes
activated by STAT-5 are BCL-xL, an inhibitor of apoptosis, and fas-ligand, an activator
of apoptosis in cells expressed the fas receptor. PI3 kinase also contributes to anti-apoptotic
activity of IL-2 through AKT activation. T cell responses to IL-2 must be coordinated
in part in the complex protein-protein interactions with the IL-2 receptor beta chain.
(This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_il2rbPathway;
Origin ID : C39123;
UMLS CUI : C1512593;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
