IL-3 Signaling Pathway (Bos taurus)

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ProteinRegulation of gene expressionProteinIL-3 Signaling PathwayLigandEnzyme complexmRNAReceptorFYNENPP3BCL2HCKCXCL8MAPK1CD86FOSIL3RASYKVAV1CD69TEC1CCR3LYNMAPK8TGFB1IL5RAPPPPPPPPYWHABGRB2PRKACAINPP5DPIL3RABADPIK3R2PSTAT5BPBCL2L1SOS1CSF2RBSTAT5AMAP2K1PYWHAQPSRCPAKT1PPTPN6CRKLCBLBCL2HRASGTPJAK2PIL3RAMAPK3PRAF1PJAK1PGAB2CSF2RBPPIK3R1SHC1RAPGEF1STAT3PTPN11PPIK3CDMAPK1FOSMAPK3PJUNSTAT5BPSTAT5APSTAT3CYNUCYNUCYNUCYNUInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageIL3


Description

Interleukin 3 (IL-3) is a potent growth factor belonging to the super family of cytokines. IL-3 is a 20- 32kDa glycoprotein involved in the process of hematopoiesis. It is involved in the proliferation and differentiation of pleuripotent hematopoietic stem cells, progenitor cells and their mature progeny. IL-3 is a growth factor for B lymphocytes. It also activates monocytes and augments survival and propagation of mast cells, eosinophils and stromal cells. IL-3 is secreted predominantly by activated T lymphocytes in response to immunological stimuli and to a lesser extent by mast cells and eosinophils. IL-3 exerts influence on different biological activities, primarily hematopoiesis by associating with the IL-3 receptor. This receptor is a heterodimeric complex and consists of an alpha chain- IL3RA and a beta chain CSF2RB, shared with the receptors for granulocyte macrophage colony stimulating factor and Interleukin-5. When IL-3 binds to CSF2RB receptor, adapter proteins like SHC1, GRB2 and SOS1 are recruited to activate HRAS. HRAS stimulates RAF1 which further activates MAP2K1 and finally MAPK1 and MAPK3. The signals generated through this pathway are then transmitted to the nucleus leading to the activation of various transcription factors such as JUN and FOS which are involved in the regulation of cell growth and differentiation. IL-3 mediated activation of HRAS also inhibits apoptosis through phosphatidyl inositol 3 kinase/ AKT pathway. The activation of AKT1 in response to IL-3 stimulation leads to the phosphorylation of the apoptotic regulator, BCL2-associated agonist of cell death (BAD), its binding to 14-3-3 and sequestration into the cytoplasm. IL-3 stimulation activates Janus kinase 2 (JAK2) by its phosphorylation. JAK2 in turn phosphorylates signal transducer and activator of transcription 5A and 5B. These translocate to the nucleus, serving the purpose of transcription factor for early genes as well as a feedback inhibitor of the JAK-STAT pathway. IL-3, in addition, is known to activate various tyrosine kinases such as LYN, FYN, SRC, SYK, TEC1 and HCK. The interactions and intersections between canonical and noncanonical IL-3 signaling systems are depicted in the pathway map.


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 WP286(78583) with a 88.0% conversion rate.

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Ontology Terms

 

Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
80932view15:31, 30 June 2015Mkutmonhomology conversion
63382view23:07, 9 May 2013MaintBotUpdated to 2013 gpml schema
40554view19:31, 1 March 2011MaintBotRemoved redundant pathway information and comments
35793view06:55, 13 February 2010MaintBotAdded description
33793view00:13, 9 December 2009MaintBotAutomatic update of empty xrefs
32504view12:49, 17 August 2009MaintBotFixed text labels
31202view19:33, 13 August 2009MaintBotFixed text labels
30600view22:15, 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
BADProteinENSBTAG00000012511 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
BCL2ProteinENSBTAG00000019302 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:596
BCL2L1ProteinENSBTAG00000006526 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:598
CBLProteinENSBTAG00000006817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
CCR3ProteinENSBTAG00000001338 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1232
CD69ProteinENSBTAG00000002135 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:969
CD86ProteinENSBTAG00000013118 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:942
CRKLProteinENSBTAG00000045548 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1399
CSF2RBProteinENSBTAG00000009064 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1439
CXCL8ProteinENSBTAG00000019716 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3576
ENPP3ProteinENSBTAG00000020196 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5169
FOSProteinENSBTAG00000004322 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2353
FYNProteinENSBTAG00000011851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
GAB2Protein
GRB2ProteinENSBTAG00000004736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
HCKProteinENSBTAG00000007932 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3055
HRASProteinENSBTAG00000046644 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
IL3Protein
IL3RAProtein
IL5RAProteinENSBTAG00000000273 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3568
INPP5DProteinENSBTAG00000020173 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3635
JAK1ProteinENSBTAG00000003147 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
JAK2ProteinENSBTAG00000012047 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
JUNProteinENSBTAG00000004037 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
LYNProteinENSBTAG00000020034 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4067
MAP2K1ProteinENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
MAPK8ProteinENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
PIK3CDProteinENSBTAG00000018984 (Ensembl) 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;
PRKACAProteinENSBTAG00000006642 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5566
PTPN11ProteinENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PTPN6ProteinENSBTAG00000020294 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
RAF1ProteinENSBTAG00000045748 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
RAPGEF1ProteinENSBTAG00000020791 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2889
SHC1ProteinENSBTAG00000019838 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
SOS1ProteinENSBTAG00000011643 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
SRCProteinENSBTAG00000008938 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
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
SYKProteinENSBTAG00000004767 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6850
TEC1Protein
TGFB1ProteinENSBTAG00000020457 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7040
VAV1ProteinENSBTAG00000039160 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
YWHABProteinENSBTAG00000016846 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7529
YWHAQProteinENSBTAG00000002108 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10971

Annotated Interactions

No annotated interactions
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