Gene Report

Basic Information

Approved Symbol	IL6
Approved Name	interleukin 6 (interferon, beta 2)
Previous Symbol	IFNB2
Symbol Alias	IL-6, BSF2, HGF, HSF
Location	7p21-p15
Position	chr7:22766766-22771621 (+)
External Links	Entrez Gene: 3569 Ensembl: ENSG00000136244 UCSC: uc003svj.4 HGNC ID: 6018
No. of Studies (Positive/Negative)	1(0/1)
Type	Literature-origin; Protein mapped

Positive relationships between IL6 and MDD (count: 0)

Positive relationships between IL6 and other components at different levels (count: 0)

Positive relationship network of IL6 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between IL6 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
IL6	Hong CJ, 2005	Patients and nomal controls		No significant differences were demonstrated for the genoty...... No significant differences were demonstrated for the genotype or allele frequency of the IL-6 polymorphism when comparing the MDD and control groups More...

Negative relationships between IL6 and other components at different levels (count: 0)

IL6 related SNPs in MK4MDD (count: 0)

IL6 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Interleukin-6	P05231	17(15/2)	Literature-origin

IL6 related GO terms (count: 95)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006954	inflammatory response	biological process	IDA[10443688]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0060445	branching involved in salivary gland morphogenesis	biological process	IEA
GO:0031175	neuron projection development	biological process	IMP[3264880]
GO:0006469	negative regulation of protein kinase activity	biological process	IEA
GO:0016049	cell growth	biological process	IEA
GO:0007568	aging	biological process	IEA
GO:0033138	positive regulation of peptidyl-serine phosphorylation	biological process	IDA[7508917]
GO:0042102	positive regulation of T cell proliferation	biological process	IDA[3130269]
GO:0008083	growth factor activity	molecular function	IDA[2261637]
GO:0002446	neutrophil mediated immunity	biological process	IC[16034137]
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	IEA
GO:0002690	positive regulation of leukocyte chemotaxis	biological process	IC[16034137]
GO:0033160	positive regulation of protein import into nucleus, translocation	biological process	IEA
GO:0046849	bone remodeling	biological process	IEA
GO:0045429	positive regulation of nitric oxide biosynthetic process	biological process	IEA
GO:0008360	regulation of cell shape	biological process	IEA
GO:0009408	response to heat	biological process	IEA
GO:0050829	defense response to Gram-negative bacterium	biological process	IEP[16034137]
GO:0045079	negative regulation of chemokine biosynthetic process	biological process	ISS
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IDA[17324931]
GO:1901215	negative regulation of neuron death	biological process	IEA
GO:0032496	response to lipopolysaccharide	biological process	IEA
GO:0032868	response to insulin stimulus	biological process	IEA
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation	biological process	IDA[7508917]
GO:0050710	negative regulation of cytokine secretion	biological process	IEA
GO:0045765	regulation of angiogenesis	biological process	IC[8557680]
GO:0032722	positive regulation of chemokine production	biological process	IDA[10510402]; IMP[16034137]
GO:0005576	extracellular region	cellular component	TAS
GO:0032494	response to peptidoglycan	biological process	IEP[16034137]
GO:0030168	platelet activation	biological process	TAS[7831669]
GO:0042832	defense response to protozoan	biological process	IEA
GO:0042110	T cell activation	biological process	IEA
GO:0005138	interleukin-6 receptor binding	molecular function	IPI[12829785]; IPI[12829785]; NAS[1883960]
GO:0050871	positive regulation of B cell activation	biological process	IDA[3491322]
GO:0045599	negative regulation of fat cell differentiation	biological process	NAS[16464856]
GO:0051384	response to glucocorticoid stimulus	biological process	IDA[10443688]
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity	biological process	IDA[7749983]
GO:0005615	extracellular space	cellular component	IDA[3023045]
GO:0051024	positive regulation of immunoglobulin secretion	biological process	IDA[3491322]
GO:0001781	neutrophil apoptotic process	biological process	IDA[7595060]
GO:0045666	positive regulation of neuron differentiation	biological process	IEA
GO:0043200	response to amino acid stimulus	biological process	IEA
GO:0051607	defense response to virus	biological process	IDA[3023045]
GO:0046888	negative regulation of hormone secretion	biological process	IEA
GO:0045721	negative regulation of gluconeogenesis	biological process	IEA
GO:0006959	humoral immune response	biological process	IC[3491322]
GO:0050679	positive regulation of epithelial cell proliferation	biological process	IEA
GO:0009409	response to cold	biological process	IEA
GO:0010888	negative regulation of lipid storage	biological process	NAS[16464856]
GO:0043154	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	biological process	IEA
GO:0002548	monocyte chemotaxis	biological process	IC[10510402]
GO:0019221	cytokine-mediated signaling pathway	biological process	IDA[2261637]
GO:0051897	positive regulation of protein kinase B signaling cascade	biological process	IEA
GO:0031018	endocrine pancreas development	biological process	ISS[18719127]
GO:0042493	response to drug	biological process	IEA
GO:0009897	external side of plasma membrane	cellular component	IEA
GO:0046677	response to antibiotic	biological process	IEA
GO:0070301	cellular response to hydrogen peroxide	biological process	IDA[19168699]
GO:0045740	positive regulation of DNA replication	biological process	IEA
GO:0046716	muscle cell homeostasis	biological process	IEA
GO:0045454	cell redox homeostasis	biological process	IEA
GO:0048635	negative regulation of muscle organ development	biological process	IEA
GO:0042981	regulation of apoptotic process	biological process	IDA[9949178]
GO:0008284	positive regulation of cell proliferation	biological process	IDA[2261637]; IMP[18719127]
GO:0032966	negative regulation of collagen biosynthetic process	biological process	IDA[12419823]
GO:0043066	negative regulation of apoptotic process	biological process	IDA[7595060]; IMP[18719127]
GO:0045727	positive regulation of translation	biological process	IDA[16732314]
GO:0005896	interleukin-6 receptor complex	cellular component	IDA[2261637]
GO:0009612	response to mechanical stimulus	biological process	IEA
GO:0043410	positive regulation of MAPK cascade	biological process	IDA[12419823]
GO:0070102	interleukin-6-mediated signaling pathway	biological process	IDA[12552091]
GO:0045669	positive regulation of osteoblast differentiation	biological process	TAS[12372336]
GO:0050830	defense response to Gram-positive bacterium	biological process	IEP[16034137]
GO:0032755	positive regulation of interleukin-6 production	biological process	IDA[10510402]
GO:0005125	cytokine activity	molecular function	IDA[3023045]; NAS[10443688]
GO:0051602	response to electrical stimulus	biological process	IEA
GO:0008285	negative regulation of cell proliferation	biological process	IEA
GO:0002675	positive regulation of acute inflammatory response	biological process	IDA[2444978]
GO:0048661	positive regulation of smooth muscle cell proliferation	biological process	IDA[10510402]
GO:0070091	glucagon secretion	biological process	ISS[18719127]
GO:0060664	epithelial cell proliferation involved in salivary gland morphogenesis	biological process	IEA
GO:0042517	positive regulation of tyrosine phosphorylation of Stat3 protein	biological process	IDA[12643274]
GO:0046427	positive regulation of JAK-STAT cascade	biological process	IDA[17324931]
GO:2000366	positive regulation of STAT protein import into nucleus	biological process	IC[17324931]
GO:0045630	positive regulation of T-helper 2 cell differentiation	biological process	IEA
GO:0045893	positive regulation of transcription, DNA-dependent	biological process	IDA[7749983]
GO:0051971	positive regulation of transmission of nerve impulse	biological process	IEA
GO:0002384	hepatic immune response	biological process	IDA[2444978]; TAS[12832423]
GO:0031000	response to caffeine	biological process	IEA
GO:0010574	regulation of vascular endothelial growth factor production	biological process	IDA[8557680]
GO:0051592	response to calcium ion	biological process	IEA
GO:0045188	regulation of circadian sleep/wake cycle, non-REM sleep	biological process	IEA
GO:0006953	acute-phase response	biological process	TAS[12832423]
GO:0051092	positive regulation of NF-kappaB transcription factor activity	biological process	IDA[12419823]
GO:0031667	response to nutrient levels	biological process	IEA

IL6 related KEGG pathways (count: 11)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa05332	graft versus_host_disease	Graft-versus-host disease	Graft-versus-host disease (GVHD) pathophysiology can be summ...... Graft-versus-host disease (GVHD) pathophysiology can be summerized in a three-step process. During step 1, the conditioning regimen (irradiation and/or chemotherapy) leads to damage, activation of host tissues and induction of inflammatory cytokines secretion. Increased expression of major histocompatibility complex (MHC) antigens and adhesion molecules leads to enhancement of the recognition of host MHC and/or minor histocompatibility antigens by mature donor T cells. Donor T-cell activation in step II is characterized by the predominance of Th1 cells and the secretion of IL-2 and IFN-gamma. These cytokines induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. Lipopolysaccharide (LPS), which leaks through the intestinal mucosa that was damaged during step 1, together with IFN-gamma, from step 2, further stimulate macrophages to secrete cytokines and NO. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05020	prion diseases	Prion diseases	Prion diseases, also termed transmissible spongiform encepha...... Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to occur after PrPC has reached the plasma membrane or is re-internalized for degradation. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. Pathways that may lead to neuronal death comprise oxidative stress, regulated activation of complement, ubiquitin-proteasome and endosomal-lysosomal systems, synaptic alterations and dendritic atrophy, corticosteroid response, and endoplasmic reticulum stress. In addition, the conformational transition could lead to the lost of a beneficial activity of the natively folded protein, PrPC. More...
hsa04623	cytosolic dna_sensing_pathway	Cytosolic DNA-sensing pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified sensor of cytosolic DNA which activates the IRF and NF-{kappa}B transcription factors, leading to production of type I interferon and other cytokines. The second type of cytoplasmic DNA sensor is AIM2. Upon sensing DNA, AIM2 triggers the assembly of the inflammasome, culminating in interleukin maturation. In addition to these receptors, there is a mechanism to sense foreign DNA, with the host RNA polymerase III converting the DNA into RNA for recognition by the RNA sensor RIG-I. These pathways provide various means to alert the cell. More...
hsa04621	nod like_receptor_signaling_pathway	NOD-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. These NLRs include NALP1, NALP3 and Ipaf. The inflammasomes are critical for generating mature proinflammatory cytokines in concert with Toll-like receptor signaling pathway. More...
hsa04630	jak stat_signaling_pathway	Jak-STAT signaling pathway	The Janus kinase/signal transducers and activators of transc...... The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors. More...
hsa05410	hypertrophic cardiomyopathy_hcm	Hypertrophic cardiomyopathy (HCM)	Hypertrophic cardiomyopathy (HCM) is a primary myocardial di...... Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in 11 genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction. More...
hsa05200	pathways in_cancer	Pathways in cancer
hsa04640	hematopoietic cell_lineage	Hematopoietic cell lineage	Blood-cell development progresses from a hematopoietic stem ...... Blood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid progenitor (CLP) or a common myeloid progenitor (CMP). A CLP gives rise to the lymphoid lineage of white blood cells or leukocytes-the natural killer (NK) cells and the T and B lymphocytes. A CMP gives rise to the myeloid lineage, which comprises the rest of the leukocytes, the erythrocytes (red blood cells), and the megakaryocytes that produce platelets important in blood clotting. Cells undergoing these differentiation process express a stage- and lineage-specific set of surface markers. Therefore cellular stages are identified by the specific expression patterns of these genes. More...
hsa04060	cytokine cytokine_receptor_interaction	Cytokine-cytokine receptor interaction	Cytokines are soluble extracellular proteins or glycoprotein...... Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Cytokines are released by various cells in the body, usually in response to an activating stimulus, and they induce responses through binding to specific receptors on the cell surface of target cells. Cytokines can be grouped by structure into different families and their receptors can likewise be grouped. More...
hsa04672	intestinal immune_network_for_iga_production	Intestinal immune network for IgA production	The intestine is the largest lymphoid tissue in the body. On...... The intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies that serve as the first line of defense against microorganisms. The basic map of IgA production includes induction of mucosal B cells in the Peyer's patches, circulation through the bloodstream and homing to intestinal mucosa of IgA-commited plasma cells, and local antibody production for export across the intestinal membranes. Multiple cytokines, including TGF-{beta}, IL-10, IL-4, IL-5, and IL-6, are required to promote IgA class switching and terminal differentiation process of the B cells. Secreted IgA promotes immune exclusion by entrapping dietary antigens and microorganisms in the mucus and functions for neutralization of toxins and pathogenic microbes. More...
hsa04620	toll like_receptor_signaling_pathway	Toll-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK. More...

IL6 related BioCarta pathways (count: 11)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
IL17_PATHWAY	il17 pathway	IL 17 Signaling Pathway	Inflammation is a complex response involving many different ...... Inflammation is a complex response involving many different cells and signaling molecules, including the secretion of the cytokine IL-17 by activated T cells. IL-17 secretion is restricted to specific subsets of T cells but the receptor for IL-17 is widely expressed throughout the body, including fibroblasts and epithelial cells. Inflammatory responses involving IL-17 probably contribute to arthritis, asthma, skin immune reactions and autoimmune disorders. Fibroblasts and other cells stimulated by IL-17 are induced themselves to secrete inflammatory and hematopoietic cytokines, including IL-6, IL-8, G-CSF and Stem Cell Factor (SCF). These cytokines in turn provoke a range of activities, including the stimulation of neutrophil proliferation and differentiation. More...
IL6_PATHWAY	il6 pathway	IL 6 signaling pathway	Interleukin-6 (IL-6) is a cytokine that provokes a broad ran...... Interleukin-6 (IL-6) is a cytokine that provokes a broad range of cellular and physiological responses. In addition to playing a role in inflammation and hematopoiesis, IL-6 is involved in other processes such as neuronal differentiation and bone loss. To produce these effects IL-6 signals through a receptor composed of two different subunits, an alpha subunit that produces ligand specificity and gp130, a receptor subunit shared in common with other cytokines in the IL-6 family. Binding of IL-6 to its receptor initiates cellular events including activation of JAK kinases and activation of ras-mediated signaling. Activated JAK kinases phosphorylate and activate STAT transcription factors, particularly STAT3, that move into the nucleus to activate transcription of genes containing STAT3 response elements. The ras-mediated pathway, acting through Shc, Grb-2 and Sos-1 upstream and activating Map kinases downstream, activates transcription factors such as ELK-1 and NF-IL-6 (C/EBP-beta) that can act through their own cognate response elements in the genome. These factors and other transcription factors like AP-1 and SRF (serum response factor) that respond to many different signaling pathways come together to regulate a variety of complex promoters and enhancers that respond to IL-6 and other signaling factors. More...
IL10_PATHWAY	il10 pathway	IL-10 Anti-inflammatory Signaling Pathway	IL-10 is a cytokine with potent anti-inflammatory properties...... IL-10 is a cytokine with potent anti-inflammatory properties, repressing the expression of inflammatory cytokines such as TNF-alpha, IL-6 and IL-1 by activated macrophages. The IL-10 receptor is in the JAK/STAT class of receptors but activation of the JAK/STAT pathways by IL-10 does not appear on its own to be responsible for the anti-inflammatory properties of this cytokine. The anti-inflammatory actions of IL-10 appear to require induction of the enzyme heme oxygenase-1 (HO-1) through a map kinase pathway involving the p38 kinases. HO-1 is involved in the biosynthesis of heme, and catalyzes a reaction producing carbon monoxide, free iron, and the heme precursor biliverdin. HO-1 is induced by IL-10 and is also induced by oxidative stress. Blocking HO-1 with inhibitors or antisense blocks the anti-inflammatory actions of IL-10. The anti-inflammatory actions of HO-1 appear to be the result of signaling by carbon monoxide it produces since removal of CO blocks the anti-inflammatory action of IL-10 and HO-1. The anti-inflammatory actions of IL-10 may be therapeutically useful either directly or through modulation of HO-1 activity. More...
ERYTH_PATHWAY	eryth pathway	Erythrocyte Differentiation Pathway	Stem cells in the bone marrow produce a variety of hematopoi...... Stem cells in the bone marrow produce a variety of hematopoietic cell types from common progenitor cells under the influence of cytokines and growth factors. CFU-GEMM cells are a key intermediate in the differentiation of granulocytes, erythrocytes, monocytes and megakaryocytes. Erythropoietin (EPO) is a cytokine produced in the kidneys that, along with other cytokines, induces red blood cell (erythrocyte) differentiation in the bone marrow from CFU-GEMM cells. As the erythrocyte lineage progresses, cells lose their nuclei, and move out of the bone marrow into circulation. The ability of EPO to selectively induce red blood cell differentiation has allowed extensive therapeutic use of the recombinant form of this cytokine to treat anemias. More...
STEM_PATHWAY	stem pathway	Regulation of hematopoiesis by cytokines	The process of hematopoesis is regulated by various cytokine...... The process of hematopoesis is regulated by various cytokines. The combination of cytokines stimulates the proliferation and/or differentiation of the various hematopoietic cell types. Bone marrow stromal cells are the major source of hematopoietic cytokines in the non-infecteous state. In the presence of infection, cytokines produced by activated macrophages and TH cells induce hematopoietic activity. The induction by cytokines results in rapid expansion of the population of white blood cells to fight infection. The specific cytokines that affect a step of cell differentiation are placed adjacent to the arrow representing that step. Lines with ? indicate likely, but still hypothetical pathways. More...
HER2_PATHWAY	her2 pathway	Role of ERBB2 in Signal Transduction and Oncology	Her2 or ERBB2 belongs to a class of proteins having high hom...... Her2 or ERBB2 belongs to a class of proteins having high homology with epidermal growth factor receptor (EGFR or ERBB1). It encodes a protein with the molecular weight of 185 KDa. Unlike other members of EGFR family, no ligand for Her2 has been found and it usually associates with members of ERBB1 family to form functional heterodimers. It has been shown that it can form dimers with ERBB (EGFR), ERBB3 and ERBB4 as well as gp130 subunits of IL-6 receptor. In at least some cell types, the association between gp130 and HRBB2 is essential for HRBB2-ERBB3 phosphorylation and subsequent MAP kinase signaling. Although ERBB1 can form homodimers, the signaling for ERBB1 is usually transient and the receptor undergoes internalization after ligand binding and activation. EGFR-HER2 complex increases the signaling capacity of EGFR by increasing the ligand affinity as well as the recycling of the heterodimer. Of all the ERBB heterodimers, ERBB2-ERBB3 heterodimers perhaps elicit the strongest signal. Removing ERBB3 from the cell has a drastic effect on ERBB2 mediated signaling and downstream effectors. The clinical importance of HER2 cannot be overstated. In addition, monoclonal antibody (Herceptin) against this receptor has been shown to be an effective treatment of breast cancer patients who have a high level of HER2 over expression. More...
CYTOKINE_PATHWAY	cytokine pathway	Cytokine Network	Several different cell types coordinate their efforts as par...... Several different cell types coordinate their efforts as part of the immune system, including B cells, T cells, macrophages, neutrophils, basophils and eosinophils. Each of these cell types has a distinct role in the immune system, and communicates with other immune cells using secreted factors called cytokines, including interleukins, TNF, and the interferons. Macrophages phagocytose foreign bodies and are antigen-presenting cells, using cytokines to stimulate specific antigen dependent responses by B and T cells and non-specific responses by other cell types. T cells secrete a variety of factors to coordinate and stimulate immune responses to specific antigen, such as the role of helper T cells in B cell activation in response to antigen. The proliferation and activation of eosinophils, neutrophils and basophils respond to cytokines as well. Cytokine communication is often local, within a tissue or between cells in close proximity. Each of the cytokines is secreted by one set of cells and provokes a response in another target set of cells, often including the cell that secretes the cytokine. Some cytokines, like IL-1, interferons and TNF, stimulate a broad inflammatory response in response to infection or injury. Other cytokines have more specific functions such the following examples. IL-2 stimulates the proliferation and activation of B and T cells. IL-4 plays a role in the differentiation of Th2 cells, in allergic responses, and in the switching of antibody types. IL-5 stimulates the production and maturation of eosinophils during inflammation. IL-8 is a chemokine, a chemotactic factor that attracts neutrophils, basophils and T cells to sites of inflammation. IL-12 and IL-18 are involved in helper T cell differentiation. IL-10 apparently acts to repress secretion of proinflammatory cytokines. The complex interplay of these different cytokine functions with immune cells is essential for correct immune function. More...
IL5_PATHWAY	il5 pathway	IL 5 Signaling Pathway	IL-5 is an inflammatory signaling molecule that primarily st...... IL-5 is an inflammatory signaling molecule that primarily stimulates eosinophil proliferation, maturation and activation. Eosinophils are leukocytes involved in inflammatory responses that defend against parasites and cause some aspects of asthma, allergic reactions, and perhaps autoimmune disorders. The action of IL-5 begins with an immune response in tissues, such as activation of macrophages and T cells that secrete IL-1, IL-4 and IL-6. The immune response can lead to IL-5 secretion by T cells, eosinophils and mast cells. Secreted IL-5 stimulates production and maturation of eosinophils in bone marrow that migrate to tissues in response to eotaxin and release factors that damage tissues, causing some of the undesirable consequences of inflammation. The receptor for IL-5 is a heterodimer of an alpha subunit that is required for IL-5 selective binding and a beta subunit that is also part of the IL-3 and GM-CSF receptors. Binding of IL-5 to the IL-5 receptor at the cell surface activates JAK/STAT signaling pathways that regulate transcription, proliferation, and differentiation. More...
IL1R_PATHWAY	il1r pathway	Signal transduction through IL1R	Interleukin-1 (IL-1) is a pro-inflammatory cytokine that sig...... Interleukin-1 (IL-1) is a pro-inflammatory cytokine that signals primarily through the type 1 IL-1 receptor (IL-1R1). The activities of IL-1 include induction of fever, expression of vascular adhesion molecules, and roles in arthritis and septic shock. The inflammatory activities of IL-1 are partially derived by transcriptionally inducing expression of cytokines such as TNF-alpha and interferons, as well as inducing the expression of other inflammation-related genes. There are two forms of IL-1 encoded by distinct genes, IL-1 alpha and IL-1 beta. IL-1 beta is produced as a 269 amino acid precursor that is cleaved by IL-1beta converting enzyme (ICE) to the active IL-1 beta form that is secreted. IL-1 signaling is opposed by the naturally occurring peptide IL-1 receptor antagonist which is a therapeutic agent for the treatment of arthritis. The type 1 IL-1 receptor protein binds IL-1 beta but requires the IL-1 receptor accessory protein (IL-1RAcP) to transduce a signal. IL-1 binding causes activation of two kinases, IRAK-1 and IRAK-2, associated with the IL-1 receptor complex. IRAK-1 (IL-1 Receptor Associated Kinase) activates and recruits TRAF6 to the IL-1 receptor complex. TRAF6 activates two pathways, one leading to NF-kB activation and another leading to c-jun activation. The TRAF associated protein ECSIT leads to c-Jun activation through the Map kinase/JNK signaling system. TRAF6 also signals through the TAB1/TAK1 kinases to trigger the degradation of I-kB, and activation of NF-kB. The IL-1 signaling cascade represents a highly conserved response to pathogens through evolution, with homologs in insects and even in plants. The signal transduction cascade utilized by IL-1 receptor is similar to that of TNF, resulting in NF-kB activation, and is most similar to that of the Toll-like receptors that also participate in inflammatory signaling responses to pathogen components like endotoxin. More...
INFLAM_PATHWAY	inflam pathway	Cytokines and Inflammatory Response	Inflammation is a protective response to infection by the im...... Inflammation is a protective response to infection by the immune system that requires communication between different classes of immune cells to coordinate their actions. Acute inflammation is an important part of the immune response, but chronic inappropriate inflammation can lead to destruction of tissues in autoimmune disorders and perhaps neurodegenerative or cardiovascular disease. Secreted cytokine proteins provide signals between immune cells to coordinate the inflammatory response. Some cytokines such as IL-1, IL-6 and TNF act to broadly provoke the inflammatory response while others act on specific types of immune cells. Macrophages and other phagocytotic cells provide a front-line defense against bacterial infection. Macrophages stimulate the inflammatory responses of neutrophils, fibroblasts, and endothelial cells in response infection by secreting IL-1 and TNF. IL-1 and TNF cause fever through alteration of the body temperature set-point in the hypothalamus. Fibroblasts and endothelial cells respond to IL-1 and TNF by recruiting more immune cells to the site of inflammation. Secreted IL-8 is a chemokine that attracts neutrophils to sites of infection. Macrophages also present antigen to T helper cells that play a central role in coordinating immune responses. T helper cells induce clonal expansion of T cells that respond to antigen, with IL-2 as a key mediator of T cell proliferation and activation. TGF-beta is a negative regulator of proliferation in many cells, have anti-inflammatory actions in some settings. The cytotoxic activity of Natural Killer cells (NK cells) and lymphokine activated killer cells (LAK cells) toward viral infected or tumor cells is stimulated by IL-2 and other cytokines. T helpers secrete IL-3 and IL-5 to stimulate eosinophil proliferation and activation. Eosinophils are involved in the immune response to parasitic infection. T helper cells are required to stimulate B cell responses as well, with the cytokines IL-10, IL-4 and other cytokines regulating the clonal selection and differentiation of antigen-specific B cells to form antibody-secreting plasma B cells and memory cells. In addition to inducing activation and proliferation of specific differentiated immune cells, cytokines act on hematopoeitic stem cells, causing their proliferation and differentiation into the full range of immune cells. More...
LAIR_PATHWAY	lair pathway	Cells and Molecules involved in local acute inflammatory response	Inflammation has several distinct components, including the ...... Inflammation has several distinct components, including the localized response at the site of tissue injury or infection. Tissue injury stimulates the release of inflammatory signaling molecules such as bradykinin. Bacterial infection stimulates an immune response in several ways. Bacteria that are phagocytosed can activate macrophages, causing the release of inflammatory cytokines such as IL-1, TNF, and IL-6. Bacteria can also activate the complement cascade through either the antibody-mediated pathway (classical pathway) or the alternative complement pathway. In extravascular tissues, cells that respond to infection or injury include macrophages and mast cells. Macrophages and other immune cells secrete chemokines that recruit leukocytes from the circulation to the site of inflammation. Mast cells release histamine, prostaglandins, and leukotrienes that act as chemokines, increase vascular permeability, and act on the vascular endothelium to increase tissue recruitment of leukocytes. Chemokines can recruit leukocytes or lymphocytes out of the blood stream into tissues and make blood vessels more permeable. Leukocytes are activated by inflammatory signals to express adhesion molecules that cause them to interact with the vascular endothelium, penetrate the endothelial wall and migrate into the extracellular space of tissues. The combined response of immune cells and signaling molecules at the site of inflammation induces swelling, activation of immune cells, and clearance of potential infectious agents. Chronic inflammation can however also lead to tissue damage in conditions such as arthritis, in which anti-inflammatory drugs act on various steps in inflammation to prevent disease. More...

IL6 related Reactome pathways (count: 0)

IL6 related interactors from protein-protein interaction data in HPRD (count: 5)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
IL6	PTHLH	No	in vitro	12000745
IL6	SH3GL2	No	yeast 2-hybrid	16169070
IL6	ZBTB16	Yes	yeast 2-hybrid	16169070
IL6	IL6ST	No	in vivo	14557255
IL6	IL6R	No	in vitro;in vivo	14557255 , 12829785

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped BioCarta pathways