Ligand-independent dimerization of KIT extracellular domain mutants

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Kit mutations in exon 8 and 9 affect the fifth Ig-like domain of the extracellular region, which is known to play an important role in dimer stabilization. Mutations in this region support ligand-independent dimerization of the receptor, leading to constitutive activation (Bodemer et al, 2010; Cammenga et al, 2005; Yuzawa et al, 2007; reviewed in Lennartsson and Roonstrand, 2012; Corless et al, 2011 ).
Literature References
PubMed ID Title Journal Year
23073628 Stem cell factor receptor/c-Kit: from basic science to clinical implications

Rönnstrand, L, Lennartsson, J

Physiol. Rev. 2012
19865100 Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations

Nasca, L, Lortholary, O, Sobol, H, Catteau, B, Barete, S, Stalder, JF, Grandpeix-Guyodo, C, Launay, JM, Lorette, G, Plantin, P, Georgin-Lavialle, S, Cohen-Akenine, A, Bordigoni, P, Palmérini, F, Arock, M, Dubreuil, P, Sans, B, Feger, F, Bodemer, C, Hermine, O, Yang, Y, de Prost, Y, Leventhal, PS, Skowron, F, Thomas, L, Moussy, A, Hadj-Rabia, S

J. Invest. Dermatol. 2010
22089421 Gastrointestinal stromal tumours: origin and molecular oncology

Barnett, CM, Corless, CL, Heinrich, MC

Nat. Rev. Cancer 2011
16081693 Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate

Besmer, P, Fiedler, W, Cammenga, J, Stocking, C, Horn, S, Bergholz, U, Sommer, G

Blood 2005
17662946 Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor

Mandiyan, V, Schlessinger, J, Zhang, Z, Lax, I, Yuzawa, S, Opatowsky, Y

Cell 2007
Functional status

Gain of function of extracellular domain mutants of KIT [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cite Us!