c-Kit/CD117 GNNK− Isoform Extracellular Domain (human, recombinant)

c-Kit, also known as CD117, is a type III receptor tyrosine kinase involved in the proliferation, differentiation, and survival of hematopoietic cells.^1,2 It is composed of an N-terminal extracellular domain (ECD) containing five immunoglobulin-like (Ig-like) domains, short transmembrane and juxtamembrane domains, and a C-terminal intracellular region containing the kinase domain. Alternative splicing of KIT produces two isoforms, GNNK+ and GNNK−, that contain or do not contain the tetrapeptide GNNK, respectively, in the juxtamembrane region of the ECD.³ c-Kit is expressed in hematopoietic stem and progenitor cells, as well as certain non-hematopoietic tissues.² It is activated by the binding of its ligand, stem cell factor (SCF), to the extracellular region, which induces autophosphorylation and the recruitment of signaling molecules to the intracellular region.¹ c-Kit signal transduction activates a variety of signaling pathways, including the PI3K/Akt, RAS/MAPK, and JAK/STAT pathways.^1,2 The GNNK− isoform of c-Kit undergoes more rapid autophosphorylation and internalization and shows increased MAPK signaling compared with GNNK+ c-Kit, promotes anchorage-independent growth in vitro, and induces tumorigenesis in mice.³ Homozygous knockout of Kit, the gene encoding c-Kit, is embryonic lethal, with mice developing severe anemia in utero.⁴ KIT is considered a proto-oncogene and activating mutations have been associated with a variety of cancers.^1,2 Cayman’s c-Kit/CD117 GNNK− Isoform Extracellular Domain (human, recombinant) protein consists of 502 amino acids, has a calculated molecular weight of 56.7 kDa, and a predicted N-terminus of Gln26 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is 86 kDa due to glycosylation.

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1. Roskoski, R., Jr. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol. Res. 94, 9-25 (2015).

2. Edling, C.E., and Hallberg, B. c-Kit—a hematopoietic cell essential receptor tyrosine kinase. Int. J. Biochem. Cell Biol. 39(11), 1995-1998 (2007).

3. Caruana, G., Cambareri, A.C., and Ashman, L.K. Isoforms of c-KIT differ in activation of signalling pathways and transformation of NIH3T3 fibroblasts. Oncogene 18(40), 5573-5581 (1999).

4. Russell, E.S. Hereditary anemias of the mouse: A review for geneticists. Adv. Genet. 20, 357-459 (1979).