Signaling by SCF-KIT

Stable Identifier
R-HSA-1433557
Type
Pathway
Species
Homo sapiens
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Stem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival and differentiation of hematopoetic progenitors, melanocytes and germ cells.(Linnekin 1999, Ronnstrand 2004, Lennartsson and Ronnstrand 2006). The receptor for SCF is KIT, a tyrosine kinase receptor (RTK) closely related to the receptors for platelet derived growth factor receptor, colony stimulating factor 1 (Linnekin 1999) and Flt3 (Rosnet et al. 1991). Four isoforms of c-Kit have been identified in humans. Alternative splicing results in isoforms of KIT differing in the presence or absence of four residues (GNNK) in the extracellular region. This occurs due to the use of an alternate 5' splice donor site. These GNNK+ and GNNK- variants are co-expressed in most tissues; the GNNK- form predominates and was more strongly tyrosine-phosphorylated and more rapidly internalized (Ronnstrand 2004). There are also splice variants that arise from alternative usage of splice acceptor site resulting in the presence or absence of a serine residue (Crosier et al., 1993). Finally, there is an alternative shorter transcript of KIT expressed in postmeiotic germ cells in the testis which encodes a truncated KIT consisting only of the second part of the kinase domain and thus lackig the extracellular and transmembrane domains as well as the first part of the kinase domain (Rossi et al. 1991). Binding of SCF homodimers to KIT results in KIT homodimerization followed by activation of its intrinsic tyrosine kinase activity. KIT stimulation activates a wide array of signalling pathways including MAPK, PI3K and JAK/STAT (Reber et al. 2006, Ronnstrand 2004). Defects of KIT in humans are associated with different genetic diseases and also in several types of cancers like mast cell leukaemia, germ cell tumours, certain subtypes of malignant melanoma and gastrointestinal tumours.

Literature References
PubMed ID Title Journal Year
16483568 Stem cell factor and its receptor c-Kit as targets for inflammatory diseases

Reber, L, Da Silva, CA, Frossard, N

Eur J Pharmacol 2006
16475976 The stem cell factor receptor/c-Kit as a drug target in cancer

Lennartsson, J, Rönnstrand, L

Curr Cancer Drug Targets 2006
15526160 Signal transduction via the stem cell factor receptor/c-Kit

Rönnstrand, L

Cell Mol Life Sci 2004
7688988 Expression of isoforms of the human receptor tyrosine kinase c-kit in leukemic cell lines and acute myeloid leukemia

Crosier, PS, Ricciardi, ST, Hall, LR, Vitas, MR, Clark, SC, Crosier, KE

Blood 1993
17350321 c-Kit--a hematopoietic cell essential receptor tyrosine kinase

Edling, CE, Hallberg, B

Int J Biochem Cell Biol 2007
19540337 Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3

Masson, K, Rönnstrand, L

Cell Signal 2009
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