IL-7 Signaling Pathway (Bos taurus)

From WikiPathways

Jump to: navigation, search
IL-7 Signaling PathwayNFkBpathwayFYNPMAP2K1PBCL2L1PTK2BPCDKN1BSTAT5ACCND1PMAP2K2PMYCGSK3BSTAT5BPPIK3R2IL2RGMAPK3PJAK1PIL7STAT5AIL7RSTAT3BADPMAPK1PPAKT1PJAK3PIK3R1PIL2RASTAT5BNUCYSTAT1PProteinProteinmRNALigandReceptorProteinProtein - protein dissociationEnzyme ComplexSmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMolecule


Description

Interleukin-7 (IL-7) was discovered in the year 1988 as a factor that enhanced the growth of murine B-cell precursors in bone marrow culture system. It was also known as lymphopoietin 1and pre-B cell factor. IL-7 plays an important role in the development of B and T cells in mouse and T cells in humans. It is also essential for mature and naive T-cell's survival and proliferation. Human IL-7 gene maps to chromosome 8 and is about 72kb in length. The protein encoded by this gene is 177 amino acids in length with a molecular weight of 20 kDa. The active form of IL-7 in humans is a glycoprotein of 25 kDa. In humans IL-7 has been shown to be produced from intestinal epithelial cells, keratinocytes , hepatic tissues, peripheral blood dendritic cells, follicular dendritic cells, endothelial cells, smooth muscle cells and fibroblasts. The IL-7 receptor consists of IL-7 receptor alpha chain (IL-7Rα) and a common gamma chain (γc). The gamma chain is also shared by IL-2, IL-4, IL-9, IL-15 and IL-21 receptors. The signaling pathways activated upon IL-7 binding to the receptor complex are JAK-STAT, PI-3 kinase and Src kinase pathways. JAK3, a protein tyrosine kinase is constitutively associated with the carboxy-terminal region of the gamma chain. Studies in mice lacking JAK3 have shown that it is required for transducing γc dependent signals. Mutations in JAK3 and γc have been shown to be associated with the autosomal recessive form of T-B + SCID. JAK1, another protein tyrosine kinase is associated with IL-7Rα chain and is activated upon IL-7 binding. JAK1 deficient mice shows severely impaired thymic development and no hematopoietic colony formation in response to IL-7. IL-7 would first bind to IL-7Rα and then associates with the gamma chain, bringing their intracellular domains bearing JAK1 and JAK3 together. JAK3 phosphorylates IL-7Rα chain creating docking sites for the transcription factors, STAT1, STAT3, and STAT5. JAK1 and JAK3 phosphorylate these STAT molecules and induces their dimerization and translocation to the nucleus where they activate specific target genes. PTK2B, a protein tyrosine kinase has been shown to be associated with JAK1 and plays an important role in the survival of thymocyte cell line. The enzymatic activity and its phosphorylation are highly induced by IL-7. PI-3 kinase pathway is also activated by IL-7 and this pathway is essential for the survival and proliferation of human T cell precursors. PI-3 kinase interacts with IL-7Rα upon IL-7 stimulation and activates its downstream target, AKT and its activation is mediated by γc. AKT in turn activates GSK3 beta and Bad, the death protein. Survival of pro T-cell survival by regulating Bad via PI3 kinase/AKT pathway is mediated by IL-7. IL-7 also mediates the downregulation of cyclin-dependent kinase inhibitor 1B through the PI-3 kinase pathway and this effect is required for cell proliferation. IL-7 also induces the phosphorylation of a Src kinase family member, Fyn which is constitutively associated with IL7RA. In addition, IL-7 induces phosphorylation of MAPK family members including MAPK1 and MAPK3.

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 WP205(80223) with a 96.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

No bibliography


History

View all...
CompareRevisionActionTimeUserComment
89853view12:21, 6 October 2016MkutmonModified description
80715view15:23, 30 June 2015Mkutmonhomology conversion
63469view17:19, 10 May 2013MaintBotUpdated to 2013 gpml schema
40605view19:34, 1 March 2011MaintBotRemoved redundant pathway information and comments
33842view00:32, 9 December 2009MaintBotAutomatic update of empty xrefs
30581view22:09, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
BADProteinENSBTAG00000012511 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
BCL2L1RnaENSBTAG00000006526 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:598
CCND1RnaENSBTAG00000017514 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:595
CDKN1BRnaENSBTAG00000018254 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1027
FYNProteinENSBTAG00000011851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
GSK3BProteinENSBTAG00000048057 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
IL2RARnaENSBTAG00000020892 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3559
IL2RGProteinENSBTAG00000007626 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3561
IL7ProteinENSBTAG00000016284 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3574
IL7RProteinENSBTAG00000019975 (Ensembl)
  • The common gamma chain augments IL-7 binding affinity and internalization of IL-7, which may explain the defects in X-linked severe combined immunodeficiency.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3575
JAK1ProteinENSBTAG00000003147 (Ensembl)
  • IL-7 stimulation induces tyrosine phosphorylation of the kinase JAK1 in human thymocytes
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK3ProteinENSBTAG00000020904 (Ensembl)
  • IL7 stimulation induces increased phosphorylation of JAK3 in normal human chondrocytes and thymocytes.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3718
MAP2K1ProteinENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2ProteinENSBTAG00000024450 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
MYCRnaENSBTAG00000008409 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4609
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PTK2BProteinENSBTAG00000005958 (Ensembl)
  • IL-7 stimulation induces the phosphorylation of PTK2B in human chondrocytes.
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2185
STAT1ProteinENSBTAG00000007867 (Ensembl)
  • IL-7 stimulation leads to tyrosine phosphorylation of STAT1 in human CD4 T cells and murine YT-5 cells
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT3ProteinENSBTAG00000021523 (Ensembl)
  • IL7 stimulation induces increased phosphorylation of STAT3 in normal human chondrocytes and T lymphoblasts.
  • 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

Annotated Interactions

No annotated interactions
Personal tools