Interaction of KIT and sSCF

Stable Identifier
R-HSA-205321
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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
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
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
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
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