IL-4 signaling pathway (Homo sapiens)

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MAPK3P1gene expressionSTAT6 dependentIL-4 Signaling PathwayBIRC5 STAT1 PHRH1 NFIL3PTPN11STAT6PCEBPB RELA TYK2PFOS GATA3 MAPK11 pNCOA3FES JAK2pSHC1 PNFKB1SOCS5RPS6KB1pEP300CEBPA CBLPPTPN6ATF2STAT6pINPP5DIRS1PIRS2PPIK3R2BADPSOCS1GAB2 MAPK14 pELK1IL4JAK1STAT5BPIL2RGAKT1PSTAT6PSOS1RELAIL4RPSTAT6PSTAT3PMAPK1PMAPK3MAPK1ppPIK3CAGRB2PIK3CDJAK3pRASA1DOK2pSTAT5APPIK3R1STAT6PSTAT6PPRKCZNFKB1PNFKBIAPIKBKBPCHUKPSOCS3STAT1 PSTAT5BPSTAT3PSTAT5APProteinProtein - protein dissociationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageReceptorProteinmRNALigandEnzyme complexCYNUCYNUCYNUCYNUCYNUCYNU


IL-4 is a glycoprotein which is composed of 129 amino acids and has a molecular weight of 20kDa. IL-4 and IL-13 are produced by CD4+ cells and exhibit significant functional overlap. Both these cytokines play a critical role in the promotion of allergic responses. IL-4 is primarily involved in promoting the differentiation and proliferation of T helper 2 (TH2) cells and the synthesis of immunoglobulin E (IgE). Apart from its role in allergic responses including asthma, IL-4 was also found to regulate retinal progenitor proliferation, rod photoreceptor differentiation, cholinergic and GABAergic amacrine differentiation and neuroprotection and survival. IL-4 was also found to have regulatory effects in a number of neurological diseases including Alzheimer's disease, Multiple sclerosis, Experimental autoimmune encephelitis. It was also found to relieve inflammatory and neuropathic pain. IL-4 is capable of exerting its biological activities through interaction with two cell surface receptor complexes - Type I IL4 receptor and Type II IL4 Receptor. Both these receptor complexes comprise of a common IL4Rα (CD124) subunit, which is also the functional receptor chain. Type I IL-4 receptor is formed by the interaction of IL4Rα subunit with IL-2γc (CD132). Type II IL-4 receptor is formed by the interaction of IL-4Rα subunit with IL-13Rα. Interaction of IL-4 with its receptor results in receptor dimerization and activation. The Type I receptors activates JAK1 and 3, which are associated with the receptor subunits. The activated JAK phosphorylates tyrosine residues the cytoplasmic tails of the receptor which then serves as docking sites for a number of adaptor or signaling molecules including STAT6. Activated STAT6 dimerizes, translocated to the nucleus and transcriptionally actives genes responsive to IL-4. Many of the key functions of IL4 allergic disorders, including TH2 cell differentiation, airway hyper responsiveness, mucus cell metaplasia and IgE synthesis are dependent on STAT6 activation. Other phosphorylated tyrosine residue bind to proteins with phospho-tyrosine binding (PTB) motifs including IRS proteins. This results in the phosphorylation of the IRS proteins, which can then potentially activate the PI3K/AKT cascade by binding to the p85 subunit of PI3K or the Ras/Raf/MEK/ERK cascade. The PI3K/AKT pathway is thought to mediate the growth and survival signals in multiple IL-4 responsive cell types including T- and B- lymphocytes and natural killer cells.

Please access this pathway at NetSlim database.

If you use this pathway, please cite the following paper:

Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

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  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C, Gollapudi SK, Tattikota SG, Mohan S, Padhukasahasram H, Subbannayya Y, Goel R, Jacob HK, Zhong J, Sekhar R, Nanjappa V, Balakrishnan L, Subbaiah R, Ramachandra YL, Rahiman BA, Prasad TS, Lin JX, Houtman JC, Desiderio S, Renauld JC, Constantinescu SN, Ohara O, Hirano T, Kubo M, Singh S, Khatri P, Draghici S, Bader GD, Sander C, Leonard WJ, Pandey A; ''NetPath: a public resource of curated signal transduction pathways.''; Genome Biol, 2010 PubMed Europe PMC Scholia


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116636view11:22, 9 May 2021EweitzModified title
116002view15:59, 28 March 2021EgonwCopied the NetPath paper to the literature list.
115983view18:11, 23 March 2021EgonwModified description
110790view17:32, 5 June 2020Joops05Modified title
108325view21:04, 6 December 2019L DupuisConverted interactions to graphical lines in legend
89828view12:06, 6 October 2016MkutmonModified description
79978view13:37, 29 April 2015Zarirepalced NEW ID for NCOA3
78576view14:50, 7 January 2015MaintBotadded missing graphIds
78053view13:03, 23 November 2014EgonwReplaced label Entrez Genes identifiers by their numeric IDs.
74009view15:25, 19 March 2014Joppe014connected lines
70016view01:50, 12 July 2013AlexanderPicoModified title
69985view21:32, 11 July 2013MaintBotupdated to 2013 schema
67378view10:44, 26 June 2013Christine ChichesterOntology Term : 'interleukin-4 signaling pathway' added !
63211view20:58, 8 May 2013MaintBotUpdating gpml version
48437view14:33, 24 May 2012NetPathModified description
45367view20:59, 7 October 2011AlexanderPicoOntology Term : 'DOID:8406' removed !
45131view00:50, 7 October 2011AlexanderPicofixed db refs
44846view09:47, 6 October 2011MartijnVanIerselOntology Term : 'Interleukin mediated signaling pathway' added !
44625view18:04, 22 September 2011Khanspersadded description
44624view18:03, 22 September 2011KhanspersUpdating content to NetSlim
44108view20:32, 24 August 2011KhanspersReverted to version '23:21, 1 March 2011' by Khanspers
44024view22:52, 22 August 2011KhanspersAdded category
44023view22:51, 22 August 2011KhanspersModified description
44022view22:49, 22 August 2011KhanspersUpdating pathway from NetSlim
41099view23:21, 1 March 2011MaintBotRemoved redundant pathway information and comments
35643view21:32, 12 February 2010KhanspersModified description
28126view19:19, 27 January 2009KhanspersCapitalized Pathway in name
21514view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:IL-4 NetPath 16]] moved to [[Pathway:WP395]]: Moved to stable identifier
8176view13:46, 7 January 2008MaintBot[[Pathway:Human:IL-4 NetPath 16]] moved to [[Pathway:Homo sapiens:IL-4 NetPath 16]]: Renaming species
7708view16:11, 18 December 2007MaintBotfixed category names
7247view12:41, 4 November 2007MaintBotAdded categories to GPML
6337view22:18, 22 May 2007A.Pandeygpml file for [[Human:IL-4_NetPath_16]]

External references


View all...
NameTypeDatabase referenceComment
AKT1Protein207 (Entrez Gene)
ATF2Protein1386 (Entrez Gene)
BADProtein572 (Entrez Gene)
BIRC5 Rna332 (Entrez Gene)
CBLProtein867 (Entrez Gene)
CEBPA Protein1050 (Entrez Gene)
CEBPB Protein1051 (Entrez Gene)
CHUKProtein1147 (Entrez Gene)
DOK2Protein9046 (Entrez Gene)
ELK1Protein2002 (Entrez Gene)
EP300Protein2033 (Entrez Gene)
FES Protein2242 (Entrez Gene)
FOS Rna2353 (Entrez Gene)
GAB2 Protein9846 (Entrez Gene)
GATA3 Rna2625 (Entrez Gene)
GRB2Protein2885 (Entrez Gene)
HRH1 Rna3269 (Entrez Gene)
IKBKBProtein3551 (Entrez Gene)
IL2RGProtein3561 (Entrez Gene) IL-4 induces the formation of a complex consisting of IL-4 receptor alpha and common gamma chain.
IL4Protein3565 (Entrez Gene)
IL4RProtein3566 (Entrez Gene)
INPP5DProtein3635 (Entrez Gene)
IRS1Protein3667 (Entrez Gene)
IRS2Protein8660 (Entrez Gene)
JAK1Protein3716 (Entrez Gene)
JAK2Protein3717 (Entrez Gene)
JAK3Protein3718 (Entrez Gene)
MAPK11 Protein5600 (Entrez Gene)
MAPK14 Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
NCOA3Protein2316 (Entrez Gene)
NFIL3Rna4783 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene)
PIK3CAProtein5290 (Entrez Gene)
PIK3CDProtein5293 (Entrez Gene) IL-4 induces the interaction of PIK3CD,PIK3CA with PIK3R1,PIK3R2 in human neutrophils.
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PRKCZProtein3716 (Entrez Gene)
PTPN11Protein5781 (Entrez Gene)
PTPN6Protein5777 (Entrez Gene)
RASA1Protein9046 (Entrez Gene) IL-4 stimulation leads to tyrosine phosphorylation of DOK2 and subsequent interaction of DOK2 with N-terminal SH2 domain of RASA1 in 32D cells.
RELA Protein5970 (Entrez Gene)
RELAProtein2353 (Entrez Gene)
RPS6KB1GeneProduct6198 (Entrez Gene)
SHC1 Protein6464 (Entrez Gene)
SOCS1Protein8651 (Entrez Gene)
SOCS3Protein9021 (Entrez Gene)
SOCS5Protein9655 (Entrez Gene)
SOS1Protein6654 (Entrez Gene)
STAT1 Protein6772 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
STAT5AProtein6776 (Entrez Gene)
STAT5BProtein6777 (Entrez Gene)
STAT6Protein6778 (Entrez Gene)
TYK2Protein7297 (Entrez Gene)

Annotated Interactions

No annotated interactions

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