Kit receptor signaling (WP304)

Homo sapiens

Kit is a cytokine receptor that belongs to the type III receptor tyrosine kinase family. It is structurally similar to platelet-derived growth factor recpetors (PDGFRs), colony stimulating factor-1 receptor and fms-like tyrosine kinase. Kit signaling is plays important role in a number of physiological processes including erythropoiesis, lymphopoiesis, mast cell development and function, megakaryopoiesis, gametogenesis and melanogenesis. Sequence alterations in the c-kit gene are found to be associated with different cancers including hematopoietic malignancies, gastrointestinal stromal tumors, germ cell tumors, small-cell lung cancer and pancreatic cancer. The primary ligand for kit receptor is stem cell factor (SCF). It is also known as Kit ligand, steel factor or mast cell growth factor. SCF is a glycosylated, non-covalent homodimer. Alternative splicing and proteolytic cleavage results in soluble and membrane bound forms of the protein. that binds to two KIT monomers. Binding of SCF to KIT results in the dimerization of the receptor and its autophsphorylation. The residues that are known to get phosphorylated upon ligand binding include Tyr568, Tyr570, Tyr703, Tyr721, Tyr730, Tyr823, Tyr 900 and Tyr936. Signaling events downstream of the KIT receptor are well studied. Among the signaling cascades that are activated are the Ras/Raf/MEK/MAPK and the PI3K/AKT/RPS6K pathways. KIT stimulation is also known to activate the JAK/STAT and PLC/PKC signaling pathways. Among the other key proteins that are regulated by KIT are the kinases BTK, TEC, LYN, SRC, FYN and JNK. Regulation of KIT receptor tyrosine kinase occurs through many mechanisms. Activated KIT receptors are degraded via CBL, a E3 ubiquitin-protein ligase. CBL induces the degradation of the receptor via the proteasome or lysosome. KIT can also be dephosphorylated and inactivated by the protein tyrosine phosphatase Shp1. Also, activation of protein kinase C results in a negative feedback loop, wherein it phosphorylates specific serine residues leading to the inactivation of KIT. Please access this pathway at [http://www.netpath.org/netslim/kit_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

Akhilesh Pandey , Kristina Hanspers , Martijn Van Iersel , NetPath , Daniela Digles , Martina Summer-Kutmon , Egon Willighagen , Lauren J. Dupuis , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

cytokine mediated signaling pathway Stem Cell Factor signaling pathway

Participants

Label Type Compact URI Comment
RPS6KA1 Protein ncbigene:6195
RPS6KA3 Protein ncbigene:6197
AKT1 Protein ncbigene:207
DOK1 Protein ncbigene:1796
CRK Protein ncbigene:1398
EP300 Protein ncbigene:2033
KITLG Protein ncbigene:4254
VAV1 Protein ncbigene:7409
GAB2 Protein ncbigene:9846
TEC Protein ncbigene:7006
MAP2K2 Protein ncbigene:5605
GRB7 Protein ncbigene:2886
SHC1 Protein ncbigene:6464
SH2B2 Protein ncbigene:10603
FYN Protein ncbigene:2534
KIT Protein ncbigene:3815
CRKL Protein ncbigene:1399
JAK2 Protein ncbigene:3717
PIK3R2 Protein ncbigene:5296
STAT5B Protein ncbigene:6777
SOCS1 Protein ncbigene:8651
PLCG1 Protein ncbigene:5335
BTK Protein ncbigene:695
GRB10 Protein ncbigene:2887
LYN Protein ncbigene:4067
MATK Protein ncbigene:4145
PTPN6 Protein ncbigene:5777
CBL Protein ncbigene:867
SOCS6 Protein ncbigene:9306
RPS6 Protein ncbigene:6194
MTOR Protein ncbigene:4137
SOS1 Protein ncbigene:6654
RAF1 Protein ncbigene:5894
MAP2K1 Protein ncbigene:5604
INPP5D Protein ncbigene:3635
STAT3 Protein ncbigene:6774
STAT1 Protein ncbigene:6772
MAPK1 Protein ncbigene:5594
FOXO3A Protein ncbigene:2309
GRB2 Protein ncbigene:2885
MAPK3 Protein ncbigene:5595
PTPN11 Protein ncbigene:5781
RPS6KB1 Protein ncbigene:6198
STAT5A Protein ncbigene:6776
PRKCA Protein ncbigene:5578
BAD Protein ncbigene:572
PRKCB1 Protein ncbigene:5579
MAPK8 Protein ncbigene:5599
MAPK14 Protein ncbigene:1432
PIK3R1 Protein ncbigene:5295
SRC Protein ncbigene:6714
MITF Protein ncbigene:4286
HRAS Protein ncbigene:3265

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