CD130 IL6ST (interleukin 6 signal transducer), gp130, CDw130, IL-6Rβ
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Plasma Cell
Myeloma
Leukocyte
Epithelial Cell
Neural Cell
Fibroblast
Hematopoietic Cell
Progenitor Cell
Megakaryocyte
Macrophage
Hepatocyte
Adipocyte
Muscle Cell
Osteoclast
B Cell
Monocyte
T Cell
Endothelial Cell
130 / 130
140 / 140

Expression
CD130 is expressed on T cells, monocytes, endothelial cells, at high levels on activated and EBV-transformed B cells, plasma cells and myelomas but it is also present at lower levels on most leukocytes, epithelial cells, fibroblasts, hepatocytes and neural cells.

The CD number has not been assigned for IL-11R.  IL-11R is expressed on multipotential hematopoietic progenitors, megakaryocytes, B cells, macrophages, hepatocytes, adipocytes, muscle cells and osteoclasts.


Structure
MOLECULAR FAMILY NAME: Belongs to the hematopoietin superfamily.

CD130 is a single-pass type-1 896 aa glycoprotein.  It contains a N-terminal signal peptide, a 597 aa extracellular domain which contains an Ig-like C-type domain and 5 fibronectin type-3 domains, a 22 aa transmembrane domain and a 277 aa intracellular cytoplasmic domain which contains a consensus nucleotide-binding domain but has no protein kinase catalytic domain.  The 2nd and 3rd fibronectin type-3 domains in the extracellular region forms a class 1 cytokine receptor family domain.  The functional high affinity receptor for the human IL-6R is formed by non-covalent association of 2 subunits, CD126 and CD130.  CD130 does not bind IL-6R in isolation.  CD130 is structurally similar to the  CD114 (G-CSFR).

IL-11R has a functional high affinity receptor for human IL-11R which is formed by the non-covalent association of its 2 subunits, IL-11Ra chain and CD130.  The extracellular region of the IL-11Ra chain consists of a N-terminal C2-set IgSF domain, followed by a cytokine receptor domain and a fibronectin typ-3 domain, which includes the WSXWS motif, and is structurally related to CD126, the IL-6R a chain and the a  chain of the receptor for the ciliary neurotropic factor (CNTF).  CD130, which does not bind IL-11R in isolation, consists of a C2 IgSF domain, a cytokine receptor domain and 4 fibronectin type 3 domains. The 1st contains the WSXWS motif (see IL-6R).  Alternative splicing of the IL-11Ra  chain gene results in a form of the molecule which lacks the entire cytoplasmic tail.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Most cell types ~130-140 kDa ~130-140 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  A splicing variant having no transmembrane domain exists and generates a soluble form of the receptor which is able to antagonize activation of the membrane form.  The CD130 soluble form is a circulating protein present in serum.

POST-TRANSLATIONAL MODIFICATION

CD130 is modified by glycosylation of 130 kDa-140 kDa.

Ligands
CD130 provides the signaling chain for several two-chain cytokine receptors.  Of the ligands that use CD130, only oncostatin M binds CD130 directly.  CD130 binding stabilizes the CD126/IL-6R complex resulting in the formation of a high affinity receptor of kDa = 10 pM.  The mouse IL-11Ra chain has a relative low affinity for IL-11R of kDa = 10 nM and this interaction fails to transduce a biological signal.  The generation of a high affinity receptor for IL-11R of kDa = 400-800 pM is capable of signal transduction and requires coexpression of the IL-11R a chain and CD130.

LIGANDS AND MOLECULES ASSOCIATED WITH CD130
Molecule Comment
Oncostatin M The only known direct ligand for CD130
IL-6 CD126/CD130
IL-11 IL-11R/CD130
LIF(leukemia inhibitory factor) LIF-R/CD130
CNF (ciliary neurotrophic factor) LIF-R/CD130
Cardiotrophin-1 LIF-R/CD130
CD130 CD130 forms homodimer in the presence of a complex of IL-6 and its receptor or IL-11 and its receptor
LIF receptor CD130 forms heterodimer with leukemia inhibitory factor receptor in the presence of leukemia inhibitory factor, oncostatin M, cardiotrophisn-1 or a complex of ciliary neurotrophic factor and its receptor
Oncostatin M receptor b CD130 associates with oncostatin M receptor b  to generate a receptor complex that specifically interacts with oncostatin M

 

Function
CD130 is the signaling chain for IL-6, oncostatin M, LIF, IL-11,ciliary neurotrophic factor and cardiotrophin-1 receptors.  CD130 is required for transducing biological activities of IL-6R and IL-11R.  IL-6R has restricted similarity to cytokine receptors.  IL-6R is a growth factor for myelomas, B cell hybridomas, activated and EBV-transformed B cells and T cell lines.  IL-6R also induces differentiation and proliferation of hematopoietic precursors, mediates the acute phase response of hepatocytes and affects differentiation of neural cell lines.  CD130 mediates signal transduction and is Tyr phosphorylated in cells stimulated with IL-6R.  Mutational analyses indicate that a membrane-proximal cytoplasmic region is important for the signal transduction activity of CD130.  IL-11R is a growth factor for multipotential hematopoietic progenitors.  IL-11R also stimulates erythropoiesis, enhances megakaryocyte and platelet formation, promotes osteoclastogenesis, functions as a macrophage maturation/activation factor and upregulates immunoglobulin secretion from activated B cells.  IL-11R also acts on various non-hematopoietic cell types, resulting in the inhibition of lipoprotein lipase activity in adipocytes, stimulation of acute phase protein synthesis by hepatocytes and the regulation of neuronal differentiation.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD130 IN INTACT ANIMAL

Targeted disruption of CD130 in knockout mice is embryonic lethal.  It causes thinning of ventricular myocardium, reduction of hematopoietic stem cells and structural and functional defects in placenta.  Continuous activation of CD130 in the mouse causes myocardial hypertrophy, hypergammablobulinemia, mesangial proliferative glomerulonephritis and infiltration of lymphocytes in some organs. In human, multiple myeloma appears to involve CD130 and autocrine stimulation by IL-6 and oncostatin.  CD130 is required for transducing biological activities of leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNF), oncostatin M and cardiotrophin-1.


Comments

Several other cytokines, including IL-11R, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M and cardiotrophin 1 (CT-1) utilize CD130 as a common signal transducer component of their receptors.

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD130: No information.

SUBSTRATES

CD130 is not an enzyme.

ENZYMES WHICH MODIFY CD130

Molecule Comment
Jak1 Receptor associated tyrosine kinases
Jak2 Receptor associated tyrosine kinases
Tyk2 Receptor associated tyrosine kinases



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 3572P40189
MouseQ00560M83336
MouseS51619U14412
RatA44257P40190M92340
Antibodies
AM64   View Reactivity

Revised June 25, 2008


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