IL-4 signaling pathway (WP1055)

Bos taurus

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.

Authors

Martina Summer-Kutmon , Egon Willighagen , and Eric Weitz

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

interleukin-4 signaling pathway Interleukin mediated signaling pathway interleukin-4 signaling pathway Interleukin mediated signaling pathway

Participants

Label Type Compact URI Comment
RPS6KB1 GeneProduct ensembl:ENSBTAG00000016851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
STAT1 Protein ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
STAT6 Protein ensembl:ENSBTAG00000006335 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6778
RELA Protein ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
TYK2 Protein ensembl:ENSBTAG00000011698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7297
MAPK11 Protein ensembl:ENSBTAG00000030182 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5600
FLNA Protein ensembl:ENSBTAG00000011190 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2316
FES Protein ensembl:ENSBTAG00000002941 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2242
JAK2 Protein ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
NFKB1 Protein ensembl:ENSBTAG00000020270 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
SOCS5 Protein ensembl:ENSBTAG00000008987 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9655
EP300 Protein ensembl:ENSBTAG00000016198 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2033
CBL Protein ensembl:ENSBTAG00000006817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
PTPN6 Protein ensembl:ENSBTAG00000020294 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
ATF2 Protein ensembl:ENSBTAG00000002295 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1386
INPP5D Protein ensembl:ENSBTAG00000020173 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3635
IRS1 Protein ensembl:ENSBTAG00000021308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
IRS2 Protein ensembl:ENSBTAG00000012019 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8660
BAD Protein ensembl:ENSBTAG00000012511 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
SOCS1 Protein ensembl:ENSBTAG00000004386 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8651
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
ELK1 Protein ensembl:ENSBTAG00000015817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2002
IL4 Protein ensembl:ENSBTAG00000015957 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3565
JAK1 Protein ensembl:ENSBTAG00000003147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
STAT5B Protein ensembl:ENSBTAG00000010125 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
IL2RG Protein ensembl:ENSBTAG00000007626 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
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
STAT6 Protein ensembl:ENSBTAG00000006335 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6778
SOS1 Protein ensembl:ENSBTAG00000011643 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
FOS Protein ensembl:ENSBTAG00000004322 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2353
IL4R Protein ensembl:ENSBTAG00000001602 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3566
STAT3 Protein ensembl:ENSBTAG00000021523
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
PIK3CA Protein ensembl:ENSBTAG00000009232 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5290
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
PIK3CD Protein ensembl:ENSBTAG00000018984 IL-4 induces the interaction of PIK3CD,PIK3CA with PIK3R1,PIK3R2 in human neutrophils.
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5293
JAK3 Protein ensembl:ENSBTAG00000020904 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3718
DOK2 Protein ensembl:ENSBTAG00000003341 IL-4 stimulation leads to tyrosine phosphorylation of DOK2 and subsequent interaction of DOK2 with N-terminal SH2 domain of RASA1 in 32D cells.
HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9046
DOK2 Protein ensembl:ENSBTAG00000003341 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9046
STAT5A Protein ensembl:ENSBTAG00000009496 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
BIKBA Protein ensembl:ENSBTAG00000016683 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
IKBKB Protein ensembl:ENSBTAG00000007599 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
CHUK Protein ensembl:ENSBTAG00000007591 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
SOCS3 Protein ensembl:ENSBTAG00000008441 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9021
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774

References

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