CD132 

IL2Rγ (interleukin 2 receptor, γ severe combined immunodeficiency)

Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
T Cell
B Cell
Leukocyte
Hematopoietic Cell
Fibroblast
Epithelial Cell
Endothelial Cell
Bone Marrow
Lymphoid Cell
Thymocyte
Megakaryocyte
Leukemia cell
Erythroid Cell
Myeloid Cell
NK Cell
Macrophage
Neutrophil
Megakaryoblastic Cell
Granulocyte
64 / 64
70 / 70

Expression
CD132 is expressed on T and B cells, NK cells, leukocytes, monocytes, macrophages and neutrophils.  CD132 is the common g chain for CD25 (IL-2R) which is expressed on activated cells including T and B cells and monocytes, CD124 (IL-4R) which is expressed on mature B and T cells, hematopoietic precursors, fibroblasts, epithelial and endothelial cells, CD127 (IL-7R) which is expressed on bone marrow lymphoid precursors, pro-B cells, thymocytes, mature T cells and monocytes, CD129 (IL-9R) which is expressed on activated T cells, T cell lines, B cells, a megakaryoblastic leukemia cell line (Mo7E) and both erythroid and myeloid precursors and the IL-15R.  The CD number for the IL-15R has not been assigned. 

Structure
MOLECULAR FAMILY NAME: Belongs to the cytokine receptor superfamily.

CD132 (IL-2R) is a single-pass type-1 g chain 369 aa glycoprotein.   It contains a 22 aa leader sequence, an extracellular domain which contains conserved cysteine residues, a cytokine receptor domain and a fibronectin type-3 domain containing the Trp-Ser-X-TRP-Ser WSXWS motif sequence, a transmembrane domain and an 86 aa cytoplasmic tail which contains a region of limited homology to SH2 subdomain and 4 Src-related kinases. 

Receptors for a variety of interleukins are referred to belonging to a common γ chain along with CD25 (IL-2), CD124 (IL-4), CD127 (IL-7), CD129 (IL-9) and CD122 (IL-15).  CD124 forms a heterodimeric receptor complex at the cell surface through the association of CD124 and CD132.  CD127 forms a heterodimer receptor complex at the cell surface through the association of CD127 and CD132.  The functional CD129 consists of a complex formed through the association of CD129 and CD132.  The functional CD122 is a heterotrimeric receptor complex comprising the CD122 (IL-2R) a chain, CD122 (IL-2R) β chain and the common g chain CD132.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
MOLT4 64 kDa
PHA-stimulated PBL 65-70 kDa

POST TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

There is glycosylation and tyrosine phosphorylation after ligand stimulation.

Ligands
The functional high affinity of IL-2R with kDa = 10 pM is composed of a non-covalently associated CD25/CD122/CD132 heterotrimer.  CD122/CD132 heterodimer binds IL-2R with an intermediate affinity with kDa = 1 nM. The intermediate-affinity receptors are important for IL-2R signaling.

The high affinity IL-4Rs with kDa = 50-100 pM may be composed of CD124/CD132 or CD124/IL-13R a chain. IL-4R-induced  signal transduction involves IL-4R binding and activation of 2 Janus family Tyr kinases, Jak1 and Jak3.  These Tyr kinases activate signal transducers and activators of transcription Stat proteins and are denoted IL-4R Stat(s) in the case of IL-4R.  IL-4R induces association of PI 3-kinase with the mouse IL-4R.

IL-7R has 2 classes with a low affinity of kDa = 5-10 nM and a high affinity of kDa = 100 pM.  The association of CD127 and CD132 augments both IL-7R binding and internalization.

The IL-9R binds IL-9R with an affinity of kDa ~100 pM as demonstrated for the receptors on a mouse T cell clone. The complex formed between CD129 and CD132 is essential for IL-9R-dependent signal transduction.

The IL-15R a chain binds IL-15R with a high affinity of kDa = 10 pM. However, the interaction between the IL-15R a chain and CD122/CD132 is required to form a functional high affinity IL-15R which is capable of mediating signal transduction.  High concentrations of IL-15R, 450 ng/ml, can bind to, and signal through, a complex of CD122/CD132 in the absence of the IL-15R a chain. 

LIGANDS AND MOLECULES ASSOCIATED WITH CD132
Molecule Comment
IL-2 CD132 is a component of the receptors for each of these cytokines, and these cytokines can be chemically crosslinked to CD132 as part of each receptor complex; however, isolated CD132 exhibits little if any binding to any of these cytokines
IL-4 CD132 is a component of the receptors for each of these cytokines, and these cytokines can be chemically crosslinked to CD132 as part of each receptor complex; however, isolated CD132 exhibits little if any binding to any of these cytokines
IL-7 CD132 is a component of the receptors for each of these cytokines, and these cytokines can be chemically crosslinked to CD132 as part of each receptor complex; however, isolated CD132 exhibits little if any binding to any of these cytokines
IL-9 CD132 is a component of the receptors for each of these cytokines, and these cytokines can be chemically crosslinked to CD132 as part of each receptor complex; however, isolated CD132 exhibits little if any binding to any of these cytokines
IL-15 CD132 is a component of the receptors for each of these cytokines, and these cytokines can be chemically crosslinked to CD132 as part of each receptor complex; however, isolated CD132 exhibits little if any binding to any of these cytokines
CD25 (IL-2R a) High affinity IL-2R consists of CD25, CD122 and CD132
CD122 (IL-2R b) High affinity IL-2R consists of CD25, CD122 and CD132
CD124 (IL-4R a) High affinity type 1 IL-4R consists of CD124 and CD132
CD127 (IL-7R) High affinity IL-7R consists of CD127 and CD132
IL-9R Fully functional IL-9R consists of at least IL-9R and CD132
IL-15R a  High affinity type I IL-15R consists of IL-15R a, CD122 and CD132
Jak3 Jak3 kinase is constitutively associated with CD132 and activated after the stimulation with IL-2R, IL-4R, IL-7R, IL-9R and IL-15R
Jak1 Tyrosine kinase associated with and activated by some of the CD132 receptor complexes
Syk Tyrosine kinase associated with and activated by some of the CD132 receptor complexes
Lck Tyrosine kinase associated with and activated by some of the CD132 receptor complexes



Function
CD25 induces the activation and proliferation of T and B cells, thymocytes, NK cells, and macrophages.  IL-4R is a growth factor for pre-activated B and T cells.  CD124 enhances IgG1 and IgE production, differentiation of Th2-type CD4+ cells and the expression of MHC class II molecules on B cells and macrophages.  CD124 also induces macrophage activation and synergizes with colony-stimulating factors in promoting the growth of hematopoietic cells.   CD127 stimulates the proliferation of pro-B and pre-B cells, thymocytes and mature T cells and induces the activation of monocytes.  Receptor engagement stimulates Tyr phosphorylation and phosphatidylinositol turnover in B precursors and thymocytes.  CD129 promotes the growth of activated T cells and a megakaryoblastic leukemia cell line (Mo7E), and supports the generation of erythroid and myeloid precursors.  CD129 also potentiates the CD124 production of IgG and IgE from B cells.  CD129 stimulation of Mo7E cells induce Tyr phosphorylation of 4 unidentified proteins.  CD122 shares biological activities with CD25, such as the activation and proliferation of T cells, generation of cytotoxic T cells and lymphokine-activated killer (LAK) cells, and the proliferation of NK and B cells.

BIOCHEMICAL ACTIVITY

There is a ligand binding for IL-2R, IL-4R, IL-7R, IL-9R and IL-15R.  Signaling for these cytokines is coupling to Jak3.

DISEASE RELEVANCE AND FUNCTION OF CD132 IN INTACT ANIMAL

In humans, mutation in CD132 results in X-linked severe combined immunodeficiency (XSCID), a disease characterized by the absence of T and NK cells and the gene is a target for gene therapy.  Knockout mice for the CD132 gene show a broad-ranging immune deficiency involving T, B and NK lineages.  Mutations in any of the individual cytokines or specific receptor chains are associated with mild symptoms, suggesting redundancy in function, but the CD132 chain is critical to the development of the immune system.  Ligand binding induces tyrosine phosphorylation and initiates signaling through a JAK/STAT pathway.

Comments
The soluble form of mouse IL-4R binds IL-4R with a high affinity, inhibits the biological activity of IL-4R and prevents the degradation of the cytokine.  A recombinant extracellular domain of the human IL-4R is a powerful antagonist of its specific ligand.

The IL-15Ra chain mRNA is expressed on a wide range of cell types, in contrast to CD25.  Since CD122 and CD132 are essential for IL-15R signaling in hematopoietic cell types and their expression patterns are more restricted than the IL-15Ra chain, the possibility exists that the IL-15Ra chain may associate with alternative signaling subunits in other cell types.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD132: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD132

Jak3 is a candidate.

ADDITIONAL INSIGHTS

CD132 is a target molecule for gene therapy for XSCID.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3561P31785
MouseJN0592P34902L20048
Antibodies
AG184   View Reactivity
TUGh4   View Reactivity

Revised June 25, 2008


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