|CD131||CSF2Rβ (colony stimulating factor 2 receptor β low affinity granulocyte-macrophage), IL3Rβ, CDw131|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|120 / 120|
140 / 140
|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.|
|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.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
CD131 is glycosylated and tyrosine phosphorylated.
|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
|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.|
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.
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.
Database accession numbers
Revised June 25, 2008