CD131 CSF2Rβ (colony stimulating factor 2 receptor β low affinity granulocyte-macrophage), IL3Rβ, CDw131        
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
Neutrophil
Eosinophil
Fibroblast
Endothelial Cell
Myeloid Cell
Sarcoma Cell
Osteoblast
Carcinoma Cell
Promyelocyte
Breast
Lung
Macrophage
Leukemia cell
B Cell
Granulocyte
Stem Cell
120 / 120
140 / 140

Expression
CD131 a granulocyte-macrophage colony-stimulating factor receptor (GM-CSF) is expressed on monocytes, neutrophils, eosinophils, fibroblasts, stem cells and endothelial cells.  It is also present on myelocytic and promyelocytic cell lines, osteogenic sarcoma cell lines, osteoblast-like cells and breast and lung carcinoma cell lines.  There is expression on most myeloid cells including early progenitors, granulocytes and early B cells.



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

CD131 is a single-pass type-1,  b chain 897 aa  glycopeptide.  It contains a signal sequence, an extracellular domain which contains 2 cytokine receptors (members of the fibronectin type-3 domain family), a transmembrane domain and a long cytoplasmic domain which contains proline-rich and serine-rich regions.  The cytokine receptor β chain includes GM-CSF, IL-3 and IL-5.  GM-CSFR is formed by the association of CD116 and CD131, which is the b chain common to the CD123 IL-3R and CD125 IL-5R.  IL-3R is formed by the association of CD123 and a common b chain to CD131, that is also a component of the receptors for GM-CSF and IL-5R.  CD131 does not bind any of these cytokines in isolation.  The extracellular region of CD131 can be divided into 2 homologous units, each 1 containing a cytokine receptor chain and a fibronectin type-3 domain.  The cytoplasmic tail of CD131 contains Pro- and Ser-rich regions, similar to those found in other cytokine receptor subunits including CD122 IL-2R b chain, CD124 IL-4R a chain and CD114 G-CSFR.  IL-5R is formed by the association of CD125 and a common b  chain CD131 that is also a component of the receptors for IL-3R and GM-CSF.  The structure of CD131 is described in the IL-3R entry. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Myeloid cells 120-140 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD131 is glycosylated and tyrosine phosphorylated.

Ligands
CD131 is a component of the two-cain receptors for IL-3, IL-5 and GM-CSF, but it does not bind any of these cytokines by itself.  CD131, which does not bind GM-CSF, associates with CD116 to generate a high affinity receptor for GM-CSF of kDa = 30-120 pM. The GM-CSF is believed to bind and mediate phosphorylation of the Janus family Tyr kinase, Jak2. In the mouse it has been shown that CD131 is essential for signal transduction.  CD123 binds IL-3R with very low affinity of kDa = 80-90 nM, while its association with CD131 generates a high affinity receptor for IL-3R of kDa = 110-180 pM.  A 110 kDa Ser/Thr kinase that is activated following IL-3R stimulation was shown to be constitutively associated with the IL-3R.  CD125 binds IL-5R of kDa = 1 nM and associates with CD131, which does not bind IL-5R, to generate a functional high affinity receptor for IL-5R of kDa = 50-250 pM.

LIGANDS AND MOLECULES ASSOCIATED WITH CD131
Molecule Comment
CD123 (IL-3Ra CD131 associates with the a subunits of the IL-3, IL-5 and GM-CSF receptors
CD125 (IL-5Ra CD131 associates with the a subunits of the IL-3, IL-5 and GM-CSF receptors
CD116 (GM-CSFRa CD131 associates with the a subunits of the IL-3, IL-5 and GM-CSF receptors
JAK2 Tyrosine kinase associated with CD131 and tyrosine phosphorylates upon stimulation
Shc Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain. These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5
Grb2 Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain. These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5
SHP1 Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain. These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5
SHP2 Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain. These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5
PI 3 kinase Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain. These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5
Stat5 Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain. These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5

  

Function
CD131 is a key signal transducing molecule of CD123 (IL-3R), CD116 (GM-CSFR) and CD125 (IL-5R).  CD131 is termed the common β chain, because it associates either with CD116, CD123 or CD125 molecule to form a functional receptor.  CD116 promotes the growth and differentiation of neutrophils, eosinophils and monocytes from multipotential bone marrow precursors.  It is also a growth factor for the erythroid progenitors, endothelial cells, megakaryocytes and T cells.  CD116 induces the tyrosine phosphorylation of a similar set of proteins as CD123.  On binding of cytokine to the two-chain receptor, CD131 is tyrosine-phosphorylated and initiates a signaling cascade based on the JAK/STAT pathway.  CD116 activates p21 ras and induces glucose transport, ion fluxes and the expression of a variety of genes.  CD123 promotes the growth and differentiation of multipotential hematopoietic precursors and of erythroid, neutrophil, basophil, monocyte, eosinophil and megakaryocyte committed precursors.  In the mouse, CD123 also activates mast cells and pre-B cells.  IL-3R induces the Tyr phosphorylation of several proteins and activates Ras. The signaling mechanisms of the CD123 are reviewed.  CD125 promotes the growth and differentiation of eosinphil precursors and activates mature eosinophils.  Mouse CD125 is also a B growth and differentiation factor.

BIOCHEMICAL ACTIVITY

CD131 does not bind any cytokine by itself however, it is a component of high affinity with CD116, CD123 and CD125.  JAK2 tyrosine kinase is associated with CD131 and tyrosine phosphorylates upon stimulation.  Tyrosine phosphorylated CD131 binds various signaling molecules with an SH2 domain.  These include Shc, Grb2, SHP1, SHP2, PI 3 kinase and STAT5.

DISEASE RELEVANCE AND FUNCTION OF CD131 IN INTACT ANIMAL

Defects in CD131 are a cause of cogenital pulmonary alveolar proteinosis (PAP) which is am autosomal recessive fatal respiratory disease.  The targeting of the common b subunit causes alveolar proteinosis similar to the GM-CSF knockout mouse.  It also results in reduced levels of peripheral eosinophils.

Comments

In the mouse, 2 proteins with a 91% aa sequence identity have been identified, the AIC2A and the AIC2B proteins.  Both AIC2A and AIC2B can associate with the murine CD123 orthologue to form a distinct high affinity IL-3Rs. The AIC2B protein is a common component of the murine CD116, CD123 and CD125.  The overall sequence of both proteins is similar to that of human CD131.  The human CD131 gene has been mapped to the pseudoautosomal region of the X and Y chromosomes.

In vivo administration of mAbs against the CD125 inhibits eosinophilia in transgenic mice overexpressing CD125.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD131: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD131: No information.

ADDITIONAL INSIGHTS

There are 2 homologous molecules in the mouse, 1 is the same as the human CD131 and is the common b subunit of the CD116, CD123 and CD125 receptors and the other 1 is homologous to CD131 and binds mouse CD123 with a low affinity.  It forms a high affinity receptor only with the CD123 a subunit.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 1439P32927
MouseA35782P26955M34397
MouseA40091P26954M29855
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University