IL-3 signaling pathway (WP1031)

Bos taurus

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 [http://www.netpath.org/netslim/IL_3_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-3 signaling pathway Interleukin mediated signaling pathway

Participants

Label Type Compact URI Comment
IL5RA Protein ensembl:ENSBTAG00000000273 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3568
ENPP3 Protein ensembl:ENSBTAG00000020196 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5169
VAV1 Protein ensembl:ENSBTAG00000039160 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
BCL2 Protein ensembl:ENSBTAG00000019302 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:596
CD69 Protein ensembl:ENSBTAG00000002135 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:969
CCR3 Protein ensembl:ENSBTAG00000001338 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1232
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
LYN Protein ensembl:ENSBTAG00000020034 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4067
TGFB1 Protein ensembl:ENSBTAG00000020457 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7040
CXCL8 Protein ensembl:ENSBTAG00000019716 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3576
SYK Protein ensembl:ENSBTAG00000004767 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6850
FYN Protein ensembl:ENSBTAG00000011851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
CD86 Protein ensembl:ENSBTAG00000013118 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:942
HCK Protein ensembl:ENSBTAG00000007932 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3055
MAPK8 Protein ensembl:ENSBTAG00000007876 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
FOS Protein ensembl:ENSBTAG00000004322 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2353
YWHAB Protein ensembl:ENSBTAG00000016846 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7529
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
PRKACA Protein ensembl:ENSBTAG00000006642 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5566
INPP5D Protein ensembl:ENSBTAG00000020173 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3635
BAD Protein ensembl:ENSBTAG00000012511 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
STAT5B Protein ensembl:ENSBTAG00000010125 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
BCL2L1 Protein ensembl:ENSBTAG00000006526 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:598
SOS1 Protein ensembl:ENSBTAG00000011643 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
CSF2RB Protein ensembl:ENSBTAG00000009064 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1439
STAT5A Protein ensembl:ENSBTAG00000009496 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
MAP2K1 Protein ensembl:ENSBTAG00000033983 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
YWHAQ Protein ensembl:ENSBTAG00000002108 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10971
SRC Protein ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
PTPN6 Protein ensembl:ENSBTAG00000020294 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
CRKL Protein ensembl:ENSBTAG00000045548 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1399
CBL Protein ensembl:ENSBTAG00000006817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
HRAS Protein ensembl:ENSBTAG00000046644 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
JAK2 Protein ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
RAF1 Protein ensembl:ENSBTAG00000045748 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
JAK1 Protein ensembl:ENSBTAG00000003147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3716
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
RAPGEF1 Protein ensembl:ENSBTAG00000020791 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2889
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PIK3CD Protein ensembl:ENSBTAG00000018984 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5293
JUN Protein ensembl:ENSBTAG00000004037 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725

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