IL-4 Signaling Pathway (Bos taurus)

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MAPK3Pgene expressionSTAT6 dependentIL-4 Signaling PathwayBIRC5STAT1PHRH1NFIL3PTPN11STAT6PCEBPB RELATYK2PFOSGATA3MAPK11pFLNAFESJAK2pSHC1PNFKB1SOCS5RPS6KB1pEP300CEBPA CBLPPTPN6ATF2STAT6pINPP5DIRS1PIRS2PPIK3R2BADPSOCS1GAB2 MAPK14pELK1IL4JAK1STAT5BPIL2RGAKT1PSTAT6PSOS1FOSIL4RPSTAT6PSTAT3PMAPK1PMAPK1MAPK3ppPIK3CAGRB2PIK3CDJAK3pDOK2DOK2pSTAT5APPIK3R1STAT6PSTAT6PJAK1NFKB1PBIKBAPIKBKBPCHUKPSOCS3STAT1PSTAT5BPSTAT3PSTAT5APProteinProtein - protein dissociationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageReceptorProteinmRNALigandEnzyme complexCYNUCYNUCYNUCYNUCYNUCYNU


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 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, you must cite 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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP395(79978) with a 94.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
89831view12:07, 6 October 2016MkutmonOntology Term : 'Interleukin mediated signaling pathway' added !
89830view12:07, 6 October 2016MkutmonOntology Term : 'interleukin-4 signaling pathway' added !
89829view12:06, 6 October 2016MkutmonModified description
80839view15:28, 30 June 2015Mkutmonhomology conversion
63474view17:20, 10 May 2013MaintBotUpdated to 2013 gpml schema
40610view19:34, 1 March 2011MaintBotRemoved redundant pathway information and comments
33847view00:34, 9 December 2009MaintBotAutomatic update of empty xrefs
32516view12:54, 17 August 2009MaintBotFixed text labels
31214view19:38, 13 August 2009MaintBotFixed text labels
30624view22:23, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
ATF2ProteinENSBTAG00000002295 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1386
BADProteinENSBTAG00000012511 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
BIKBAProteinENSBTAG00000016683 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
BIRC5RnaENSBTAG00000013573 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:332
CBLProteinENSBTAG00000006817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
CEBPA Protein
CEBPB Protein
CHUKProteinENSBTAG00000007591 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
DOK2ProteinENSBTAG00000003341 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9046
ELK1ProteinENSBTAG00000015817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2002
EP300ProteinENSBTAG00000016198 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2033
FESProteinENSBTAG00000002941 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2242
FLNAProteinENSBTAG00000011190 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2316
FOSProteinENSBTAG00000004322 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2353
GAB2 Protein
GATA3RnaENSBTAG00000017243 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2625
GRB2ProteinENSBTAG00000004736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
HRH1RnaENSBTAG00000001447 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3269
IKBKBProteinENSBTAG00000007599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IL2RGProteinENSBTAG00000007626 (Ensembl)
  • IL-4 induces the formation of a complex consisting of IL-4 receptor alpha and common gamma chain.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3561
IL4ProteinENSBTAG00000015957 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3565
IL4RProteinENSBTAG00000001602 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3566
INPP5DProteinENSBTAG00000020173 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3635
IRS1ProteinENSBTAG00000021308 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
IRS2ProteinENSBTAG00000012019 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8660
JAK1ProteinENSBTAG00000003147 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK2ProteinENSBTAG00000012047 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
JAK3ProteinENSBTAG00000020904 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3718
MAPK11ProteinENSBTAG00000030182 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5600
MAPK14ProteinENSBTAG00000020783 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
MAPK1ProteinENSBTAG00000010312 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
NFIL3RnaENSBTAG00000017763 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4783
NFKB1ProteinENSBTAG00000020270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
PIK3CAProteinENSBTAG00000009232 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5290
PIK3CDProteinENSBTAG00000018984 (Ensembl)
  • IL-4 induces the interaction of PIK3CD,PIK3CA with PIK3R1,PIK3R2 in human neutrophils.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5293
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PTPN11ProteinENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PTPN6ProteinENSBTAG00000020294 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
RELAProteinENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RPS6KB1GeneProductENSBTAG00000016851 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
SHC1ProteinENSBTAG00000019838 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
SOCS1ProteinENSBTAG00000004386 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8651
SOCS3ProteinENSBTAG00000008441 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
SOCS5ProteinENSBTAG00000008987 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9655
SOS1ProteinENSBTAG00000011643 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
STAT1ProteinENSBTAG00000007867 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT3ProteinENSBTAG00000021523 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
STAT5AProteinENSBTAG00000009496 (Ensembl)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
STAT5BProteinENSBTAG00000010125 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
STAT6ProteinENSBTAG00000006335 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6778
TYK2ProteinENSBTAG00000011698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297

Annotated Interactions

No annotated interactions
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