PROW: CD132

PROW and IWHLDA present the GUIDE on:
CD132
Author: Kazuo Sugamura
Reviewer: Warren J. Leonard
[GUIDE BAR]

ALTERNATE NAMES FOR CD132

IL2RG [HUGO gene name]
Common cytokine receptor gamma chain
Common gamma chain

MAJOR LINKS FOR CD132

NCBI LocusLink Record: 3561
Mendelian Inheritance in Man (OMIM): 300400
Mendelian Inheritance in Man (OMIM): 308380
SwissProt annotated protein record: P31785

FUNCTION BIOCHEMICAL ACTIVITY OF CD132

Ligand binding for IL-2, IL-4, IL-7, IL-9 and IL-15. Signaling for these cytokines, coupling to Jak3*

CELLULAR FUNCTION OF CD132

Receptor for IL-2, IL-4, IL-7, IL-9 and IL-15

DISEASE RELEVANCE OF CD132 AND FUNCTION OF CD132 IN INTACT ANIMAL

Mutation in humans causes XSCID (X-linked severe combined immunodeficiency), a disease characterized by the absence of T- and NK- cells
Knockout mice for CD132 gene show severe reduction in T- and B-cell number and function, and disappearance of NK cells

STRUCTURE MOLECULAR FAMILY FOR CD132

Families in which CD132 is a member
- CD132-->class 1 cytokine receptor-->cytokine receptor superfamily-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD132

369 amino acids including 22 amino acid-leader sequence
In its extracellular domain, conserved cysteine residues with a conserved spacing between them typical of members of the cytokine receptor superfamily
A characteristic Trp-Ser-X-Trp-Ser (WSXWS) motif in its extracellular domain
Overall similarity to Fibronectin type III domain in its extracellular domain
Cytoplasmic domain of 86 amino acids, containing 4 tyrosine residues**

MOLECULAR MASS OF CD132

CELL TYPE	MW UNREDUCED	MW REDUCED	Comment
MOLT4	64 kDa
PHA-stimulated PBL	65-70 kDa

POST-TRANSCRIPTIONAL MODIFICATION OF CD132 - Unknown

POST-TRANSLATIONAL MODIFICATION OF CD132

Glycosylation
Tyrosine phosphorylation after ligand stimulation

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

SUBSTRATES FOR CD132 - No information

ENZYMES WHICH MODIFY CD132 - Jak3 is a candidate

LIGANDS FOR CD132 AND MOLECULES ASSOCIATED WITH CD132

MOLECULE	COMMENT
IL-2	See note 1
IL-4	See note 1
IL-7	See note 1
IL-9	See note 1
IL-15	See note 1
CD25 (IL-2R alpha)	High-affinity IL-2 receptor consists of CD25, CD122 and CD132
CD122 (IL-2R beta)	High-affinity IL-2 receptor consists of CD25, CD122 and CD132
CD124 (IL-4R alpha)	High-affinity type I IL-4 receptor consists of CD124 and CD132*
CD127 (IL-7R)	High-affinity IL-7 receptor consists of CD127 and CD132
IL-9R	Fully functional IL-9 receptor consists of at least IL-9R and CD132
IL-15R alpha*	High-affinity type I IL-15 receptor consists of IL-15R alpha, CD122 and CD132*
Jak3	Jak3 kinase is constitutively associated with CD132 and activated after the stimulation with IL-2, IL-4, IL-7, IL-9 and IL-15*
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*

Note 1: CD132 is a component of the receptors for each of these cytokines, and these cytokines can be chemically cross-linked to CD132 as part of each receptor complex; however, isolated CD132 exhibits little if any direct binding to any of these cytokines)**

EXPRESSION MAIN CELLULAR EXPRESSION OF CD132

T cells
B cells
NK cells
Monocytes/macrophages
Neutrophils

AUTHOR'S ADDITIONAL INSIGHTS ON CD132

CD132 is a target molecule for gene therapy for XSCID

REAGENTS CD132-SPECIFIC MABS NEWLY ASSIGNED AT SIXTH INTERNATIONAL WORKSHOP

NAME(Workshop IDs)	SOURCE or REFERENCE	COMMENT
TUGh4 (C-89)	Kazuo Sugamura, Sendai
3B5 (C-96)	Jerome Ritz, Boston
3G11 (C-97)	Jerome Ritz, Boston
AG14C (C-98)	Toshiro Shimamura, Kawasaki
AG43C (C-99)	Toshiro Shimamura, Kawasaki
AG184 (C-100)	Toshiro Shimamura, Kawasaki

SELECTION OF OTHER CD132-SPECIFIC REFERENCE MAB - No information

SELECTED REFERENCES ON CD132

REVIEWS

1. Leonard WJ The molecular basis of X-linked severe combined immunodeficiency: defective cytokine receptor signaling. Annu Rev Med 1996 47:229 PubMed

2. Leonard WJ,Shores EW,Love PE Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development. Immunol Rev 1995 148:97 ** PubMed

3. Sugamura K,Asao H,Kondo M,Tanaka N,Ishii N,Nakamura M,Takeshita T The common gamma-chain for multiple cytokine receptors. Adv Immunol 1995 59:225 PubMed

4. Sugamura K,Asao H,Kondo M,Tanaka N,Ishii N,Ohbo K,Nakamura M,Takeshita T The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol 1996 14:179 PubMed

PRIMARY CITATIONS

5. Kondo M,Takeshita T,Higuchi M,Nakamura M,Sudo T,Nishikawa S,Sugamura K Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Science 1994 263:1453 ** PubMed

6. Kondo M,Takeshita T,Ishii N,Nakamura M,Watanabe S,Arai K,Sugamura K Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science 1993 262:1874 ** PubMed

7. Noguchi M,Nakamura Y,Russell SM,Ziegler SF,Tsang M,Cao X,Leonard WJ Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science 1993 262:1877 ** PubMed

8. Noguchi M,Yi H,Rosenblatt HM,Filipovich AH,Adelstein S,Modi WS,McBride OW,Leonard WJ Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 1993 73:147 ** PubMed

9. Russell SM,Keegan AD,Harada N,Nakamura Y,Noguchi M,Leland P,Friedmann MC,Miyajima A,Puri RK,Paul WE,et al Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science 1993 262:1880 ** PubMed

10. Takeshita T,Asao H,Ohtani K,Ishii N,Kumaki S,Tanaka N,Munakata H,Nakamura M,Sugamura K Cloning of the gamma chain of the human IL-2 receptor. Science 1992 257:379 PubMed

WWW RESOURCES

* indicates ammended by reviewer, ** indicates added by reviewer

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99 mpr@mail.nih.gov