Kit receptor signaling pathway (WP1004)

Bos taurus

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

Alex Pico , Daniela Digles , Martina Summer-Kutmon , and Egon Willighagen

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

cytokine mediated signaling pathway Stem Cell Factor signaling pathway

Participants

Label Type Compact URI Comment
RPS6KA1 Protein ensembl:ENSBTAG00000014447 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6195
RPS6KA3 Protein ensembl:ENSBTAG00000017639 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6197
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
DOK1 Protein ensembl:ENSBTAG00000018579 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1796
CRK Protein ensembl:ENSBTAG00000005665 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1398
EP300 Protein ensembl:ENSBTAG00000016198 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2033
KITLG Protein ensembl:ENSBTAG00000017549 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4254
VAV1 Protein ensembl:ENSBTAG00000039160 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
TEC Protein ensembl:ENSBTAG00000005062 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7006
MAP2K2 Protein ensembl:ENSBTAG00000024450 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
GRB7 Protein ensembl:ENSBTAG00000017366 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2886
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
SH2B2 Protein ensembl:ENSBTAG00000009691 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10603
FYN Protein ensembl:ENSBTAG00000011851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
KIT Protein ensembl:ENSBTAG00000002699 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3815
CRKL Protein ensembl:ENSBTAG00000045548 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1399
JAK2 Protein ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
STAT5B Protein ensembl:ENSBTAG00000010125 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
SOCS1 Protein ensembl:ENSBTAG00000004386 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8651
PLCG1 Protein ensembl:ENSBTAG00000017584 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5335
BTK Protein ensembl:ENSBTAG00000019250 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:695
GRB10 Protein ensembl:ENSBTAG00000017086 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2887
LYN Protein ensembl:ENSBTAG00000020034 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4067
MATK Protein ensembl:ENSBTAG00000006619 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4145
PTPN6 Protein ensembl:ENSBTAG00000020294 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
CBL Protein ensembl:ENSBTAG00000006817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
SOCS6 Protein ensembl:ENSBTAG00000017412 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9306
RPS6 Protein ensembl:ENSBTAG00000014449 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
MAPT Protein ensembl:ENSBTAG00000017512 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4137
SOS1 Protein ensembl:ENSBTAG00000011643 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
RAF1 Protein ensembl:ENSBTAG00000045748 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
MAP2K1 Protein ensembl:ENSBTAG00000033983 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
INPP5D Protein ensembl:ENSBTAG00000020173 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3635
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
STAT1 Protein ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
FOXO3 Protein ensembl:ENSBTAG00000011234 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2309
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
RPS6KB1 Protein ensembl:ENSBTAG00000016851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
STAT5A Protein ensembl:ENSBTAG00000009496 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
PRKCA Protein ensembl:ENSBTAG00000001061 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5578
BAD Protein ensembl:ENSBTAG00000012511 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
PRKCB Protein ensembl:ENSBTAG00000020921 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5579
MAPK8 Protein ensembl:ENSBTAG00000007876 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
SRC Protein ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
MITF Protein ensembl:ENSBTAG00000006679 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4286
HRAS Protein ensembl:ENSBTAG00000046644 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L: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