IL-4 signaling pathway (WP395)

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 [http://www.netpath.org/netslim/IL_4_pathway.html 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.
last edited

Authors

A.Pandey, MaintBot, Khanspers, MartijnVanIersel, AlexanderPico, NetPath, Christine Chichester, Joppe014, Egonw, Zari, Mkutmon, L Dupuis, Joops05, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: interleukin-4 signaling pathway Interleukin mediated signaling pathway

Participants

Label Type Compact Identifier
MAPK3 Protein ncbigene:5595
BIRC5 Rna ncbigene:332
STAT1 Protein ncbigene:6772
HRH1 Rna ncbigene:3269
NFIL3 Rna ncbigene:4783
PTPN11 Protein ncbigene:5781
STAT6 Protein ncbigene:6778
CEBPB Protein ncbigene:1051
RELA Protein ncbigene:5970
TYK2 Protein ncbigene:7297
FOS Rna ncbigene:2353
GATA3 Rna ncbigene:2625
MAPK11 Protein ncbigene:5600
NCOA3 Protein ncbigene:2316
FES Protein ncbigene:2242
JAK2 Protein ncbigene:3717
SHC1 Protein ncbigene:6464
NFKB1 Protein ncbigene:4790
SOCS5 Protein ncbigene:9655
RPS6KB1 GeneProduct ncbigene:6198
EP300 Protein ncbigene:2033
CEBPA Protein ncbigene:1050
CBL Protein ncbigene:867
PTPN6 Protein ncbigene:5777
ATF2 Protein ncbigene:1386
STAT6 Protein ncbigene:6778
INPP5D Protein ncbigene:3635
IRS1 Protein ncbigene:3667
IRS2 Protein ncbigene:8660
PIK3R2 Protein ncbigene:5296
BAD Protein ncbigene:572
SOCS1 Protein ncbigene:8651
GAB2 Protein ncbigene:9846
MAPK14 Protein ncbigene:1432
ELK1 Protein ncbigene:2002
IL4 Protein ncbigene:3565
JAK1 Protein ncbigene:3716
STAT5B Protein ncbigene:6777
IL2RG Protein ncbigene:3561
AKT1 Protein ncbigene:207
STAT6 Protein ncbigene:6778
SOS1 Protein ncbigene:6654
RELA Protein ncbigene:2353
IL4R Protein ncbigene:3566
STAT6 Protein ncbigene:6778
STAT3 Protein ncbigene:6774
MAPK1 Protein ncbigene:5594
MAPK3 Protein ncbigene:5595
MAPK1 Protein ncbigene:5594
PIK3CA Protein ncbigene:5290
GRB2 Protein ncbigene:2885
PIK3CD Protein ncbigene:5293
JAK3 Protein ncbigene:3718
RASA1 Protein ncbigene:9046
DOK2 Protein ncbigene:9046
STAT5A Protein ncbigene:6776
PIK3R1 Protein ncbigene:5295
STAT6 Protein ncbigene:6778
STAT6 Protein ncbigene:6778
PRKCZ Protein ncbigene:3716
NFKB1 Protein ncbigene:4790
NFKBIA Protein ncbigene:4792
IKBKB Protein ncbigene:3551
CHUK Protein ncbigene:1147
SOCS3 Protein ncbigene:9021
STAT1 Protein ncbigene:6772
STAT5B Protein ncbigene:6777
STAT3 Protein ncbigene:6774
STAT5A Protein ncbigene:6776

References

  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GSS, Venugopal AK, et al. NetPath: a public resource of curated signal transduction pathways. Genome Biol. 2010 Jan 12;11(1):R3. PubMed Europe PMC Scholia