IL-4 Signaling Pathway (Homo sapiens)

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MAPK3P29, 80, 401, 454505339228, 406305219163198, 29457, 266423, 555276, 4383, 144, 221, 473228, 40637, 48757, 266399, 403210, 438234, 399263, 399176, 438313, 332264, 403224, 384, 487, 513397, 438206, 261240, 338470, 487340, 438147, 183311, 38393, 44333, 384317, 48779, 188, 221, 240, 578311, 383176, 43849, 239159, 487, 578309, 37442, 43391176, 438188, 42357, 271, 56057, 56010, 45143313, 33, 74, 217, 305...20, 146, 27320, 146, 273487, 565, 578gene expressionSTAT6 dependentIL-4 Signal Transduction PathwayBIRC5 STAT1 P66, 305HRH1 NFIL3PTPN11STAT6CEBPB RELA TYK2P397, 399FOS GATA3 MAPK11 p57, 560NCOA3FES JAK2p29, 250, 397SHC1 P147, 399NFKB1SOCS5RPS6KB1 p80, 261EP300CEBPA CBLP210, 399PTPN6ATF2STAT6p10, 214, 250, 331, 384...INPP5DIRS1P80, 334, 340, 399IRS2P79, 80, 91, 176, 188...PIK3R2BADP77, 80, 442SOCS1GAB2 MAPK14 p57, 560ELK1IL4JAK1STAT5BP305, 546IL2RG487, 513AKT1P80, 384, 421STAT6SOS1RELAIL4RP10, 384, 578STAT6STAT3P384, 565MAPK1P29, 401, 454MAPK3MAPK1pp29, 401, 45429, 80, 401, 454PIK3CAGRB2PIK3CD399, 540JAK3p10, 317, 497RASA137, 132DOK2p37, 118, 399STAT5AP384, 546PIK3R1STAT6STAT6PRKCZ10, 406NFKB1P173, 523NFKBIAP138, 173IKBKBPCHUK406, 568P406, 568SOCS3145, 523305STAT1 P66, 305STAT5BP305, 546STAT3P384, 565STAT5AP384, 546305305Enzyme complexInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationProteinmRNAProteinReceptorLigandDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavage


Description

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 IL4Ralpha (CD124) subunit, which is also the functional receptor chain. Type I IL-4 receptor is formed by the interaction of IL4Ralpha subunit with IL-2gammac (CD132). Type II IL-4 receptor is formed by the interaction of IL-4Ralpha subunit with IL-13Ralpha1.

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.

NetPath (http://www.netpath.org) is a collaborative effort between PandeyLab at Johns Hopkins University (http://pandeylab.igm.jhmi.edu) and Institute of Bioinformatics (http://www.ibioinformatics.org). This version of the pathway is available at NetSlim (http://www.netpath.org/netslim). If you use this pathway, please cite the NetPath website.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
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

DataNodes

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NameTypeDatabase referenceComment
AKT1GeneProduct207 (Entrez Gene)
ATF2GeneProduct1386 (Entrez Gene)
BADGeneProduct572 (Entrez Gene)
BIRC5 Rna332 (Entrez Gene)
CBLGeneProduct867
CEBPA GeneProduct1050 (Entrez Gene)
CEBPB GeneProduct1051 (Entrez Gene)
CHUKGeneProduct1147 (Entrez Gene)
DOK2GeneProduct9046 (Entrez Gene)
ELK1GeneProduct2002 (Entrez Gene)
EP300GeneProduct2033 (Entrez Gene)
FES GeneProduct2242 (Entrez Gene)
FOS Rna2353 (Entrez Gene)
GAB2 GeneProduct9846
GATA3 Rna2625 (Entrez Gene)
GRB2GeneProduct2885 (Entrez Gene)
HRH1 Rna3269 (Entrez Gene)
IKBKBGeneProduct3551 (Entrez Gene)
IL2RGGeneProduct3561 (Entrez Gene) IL-4 induces the formation of a complex consisting of IL-4 receptor alpha and common gamma chain.
IL4GeneProduct3565
IL4RGeneProduct3566 (Entrez Gene)
INPP5DGeneProduct3635 (Entrez Gene)
IRS1GeneProduct3667 (Entrez Gene)
IRS2GeneProduct8660 (Entrez Gene)
JAK1GeneProduct3716 (Entrez Gene)
JAK2GeneProduct3717
JAK3GeneProduct3718 (Entrez Gene)
LigandGeneProduct7040 (Entrez Gene)
MAPK11 GeneProduct5600 (Entrez Gene)
MAPK14 GeneProduct1432
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
NCOA3GeneProduct8262 (Entrez Gene)
NFIL3Rna4783 (Entrez Gene)
NFKB1GeneProduct4790 (Entrez Gene)
NFKBIAGeneProduct4792 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PIK3CDGeneProduct5293 (Entrez Gene) IL-4 induces the interaction of PIK3CD,PIK3CA with PIK3R1,PIK3R2 in human neutrophils.
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PRKCZGeneProduct3716 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
PTPN6GeneProduct5777 (Entrez Gene)
ProteinProtein5894 (Entrez Gene)
ProteinProtein
RASA1GeneProduct9046 (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 GeneProduct5970 (Entrez Gene)
RELAGeneProduct2353 (Entrez Gene)
RPS6KB1 GeneProduct
ReceptorGeneProduct7040 (Entrez Gene)
SHC1 GeneProduct6464 (Entrez Gene)
SOCS1GeneProduct8651 (Entrez Gene)
SOCS3GeneProduct9021 (Entrez Gene)
SOCS5GeneProduct9655
SOS1GeneProduct6654 (Entrez Gene)
STAT1 GeneProduct6772 (Entrez Gene)
STAT3GeneProduct6774 (Entrez Gene)
STAT5AGeneProductSTAT5A (Entrez Gene)
STAT5BGeneProductSTAT5B (Entrez Gene)
STAT6GeneProduct6778
STAT6GeneProduct6778 (Entrez Gene)
STAT6GeneProduct6778 (Entrez Gene)
TYK2GeneProduct7297 (Entrez Gene)
mRNAProtein

Annotated Interactions

No annotated interactions

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