Reactome | Interaction of KIT and sSCF

Interaction of KIT and sSCF

Stable Identifier

R-HSA-205321

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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Two human isoforms of KIT have been identified, resulting from alternative splicing. They are characterized by the presence or absence of a tetrapeptide sequence (GNNK 510-513 aa) in the extracellular part of the juxtamembrane region and designated GNNK+ (Kit) or GNNK- (KitA) (Piao et al. 1994). The isoforms are co-expressed in most tisuues, with the GNNK- form predominating (Reith et al. 1991). No difference in ligand affinity was observed (Caruana et al. 1999).
KIT belongs to the type III tyrosine kinase receptor family, with five extracellular immunoglobulin (Ig)-like domains, a single transmembrane region, an inhibitory cytoplasmic juxtamembrane domain, and a split cytoplasmic kinase domain separated by a kinase insert segment and a cytoplasmic tail (Mol et al. 2003).
Signaling by KIT occurs following SCF binding. SCF homodimers binds to the first three Ig-like domains of KIT in the regions between aa L104-D122 and R146-D153 (Mendiaz et al. 1996, Matous et al. 1996) which leads to dimerization which is further stabilized by Ig-like domains 3-4 (Yuzawa et al., 2007).

Literature References

PubMed ID	Title	Journal	Year
1375232	A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses Lev, S, Yarden, Y, Givol, D	J Biol Chem	1992
8636116	Human stem cell factor dimer forms a complex with two molecules of the extracellular domain of its receptor, Kit Philo, JS, Wen, J, Wypych, J, Schwartz, MG, Mendiaz, EA, Langley, KE	J Biol Chem	1996
16737840	Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases Hafizi, S, Dahlback, B	Cytokine Growth Factor Rev	2006
8695790	Structure-function relationships of stem cell factor: an analysis based on a series of human-murine stem cell factor chimera and the mapping of a neutralizing monoclonal antibody Matous, JV, Langley, K, Kaushansky, K	Blood	1996
9045650	Kit receptor dimerization is driven by bivalent binding of stem cell factor Lemmon, MA, Pinchasi, D, Zhou, M, Lax, I, Schlessinger, J	J Biol Chem	1997
10523834	Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts Caruana, G, Cambareri, AC, Ashman, LK	Oncogene	1999
8774734	Epitope mapping and immunoneutralization of recombinant human stem-cell factor Mendiaz, EA, Chang, DG, Boone, TC, Grant, JR, Wypych, J, Aguero, B, Egrie, JC, Langley, KE	Eur J Biochem	1996
17662946	Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor Yuzawa, S, Opatowsky, Y, Zhang, Z, Mandiyan, V, Lax, I, Schlessinger, J	Cell	2007
7506952	Expression of the Kit and KitA receptor isoforms in human acute myelogenous leukemia Piao, X, Curtis, JE, Minkin, S, Minden, MD, Bernstein, A	Blood	1994
10884405	Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation Zhang, Z, Zhang, R, Joachimiak, A, Schlessinger, J, Kong, XP	Proc Natl Acad Sci U S A	2000
7680037	Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor Blechman, JM, Lev, S, Brizzi, MF, Leitner, O, Pegoraro, L, Givol, D, Yarden, Y	J Biol Chem	1993
12824176	Structure of a c-kit product complex reveals the basis for kinase transactivation Mol, CD, Lim, KB, Sridhar, V, Zou, H, Chien, EY, Sang, BC, Nowakowski, J, Kassel, DB, Cronin, CN, McRee, DE	J Biol Chem	2003