IL-3 signaling pathway (WP286)

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 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, NetPath, Christine Chichester, Mkutmon, L Dupuis, Egonw, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: interleukin-3 signaling pathway Interleukin mediated signaling pathway

Participants

Label Type Compact Identifier
IL3RA Protein ncbigene:3563
IL5RA Protein ncbigene:3568
ENPP3 Protein ncbigene:5169
VAV1 Protein ncbigene:7409
BCL2 Protein ncbigene:596
CD69 Protein ncbigene:969
CCR3 Protein ncbigene:1232
TEC1 Protein None
MAPK1 Protein ncbigene:5594
LYN Protein ncbigene:4067
TGFB1 Protein ncbigene:7040
IL8 Protein ncbigene:3576
SYK Protein ncbigene:6850
FYN Protein ncbigene:2534
CD86 Protein ncbigene:942
HCK Protein ncbigene:3055
MAPK8 Protein ncbigene:5599
FOS Protein ncbigene:2353
YWHAB Protein ncbigene:7529
GRB2 Protein ncbigene:2885
PRKACA Protein ncbigene:5566
INPP5D Protein ncbigene:3635
IL3RA Protein ncbigene:3563
BAD Protein ncbigene:572
PIK3R2 Protein ncbigene:5296
STAT5B Protein ncbigene:6777
BCL2L1 Protein ncbigene:598
SOS1 Protein ncbigene:6654
CSF2RB Protein ncbigene:1439
STAT5A Protein ncbigene:6776
MAP2K1 Protein ncbigene:5604
YWHAQ Protein ncbigene:10971
SRC Protein ncbigene:6714
AKT1 Protein ncbigene:207
PTPN6 Protein ncbigene:5777
CRKL Protein ncbigene:1399
CBL Protein ncbigene:867
BCL2 Protein ncbigene:596
HRAS Protein ncbigene:3265
JAK2 Protein ncbigene:3717
IL3RA Protein ncbigene:3563
MAPK3 Protein ncbigene:5595
RAF1 Protein ncbigene:5894
JAK1 Protein ncbigene:3716
GAB2 Protein ncbigene:9846
CSF2RB Protein ncbigene:1439
PIK3R1 Protein ncbigene:5295
SHC1 Protein ncbigene:6464
RAPGEF1 Protein ncbigene:2889
STAT3 Protein ncbigene:6774
PTPN11 Protein ncbigene:5781
PIK3CD Protein ncbigene:5293
MAPK1 Protein ncbigene:5594
FOS Protein ncbigene:2353
MAPK3 Protein ncbigene:5595
JUN Protein ncbigene:3725
STAT5B Protein ncbigene:6777
STAT5A Protein ncbigene:6776
STAT3 Protein ncbigene:6774
IL3 Protein ncbigene:3562

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