stem cell factor; mast-cell growth factor; c-kit ligand; steel homolog (SCF, KITLG, MGF)

Function

• ligand for c-kit receptor-type tyrosine kinase
• role in the regulation of
  • cell survival & proliferation
  • hematopoiesis
  • stem cell maintenance
  • gametogenesis
  • mast cell development, migration & function
    • enhances mast cell adhesion to fibronectin (PI-3-kinase dependent)
  • melanogenesis
• can activate several signaling pathways
  • promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, & subsequent activation of the kinase AKT1
  • transmits signals via GRB2 & activation of RAS, RAF1 & the MAP kinases MAPK1/ERK2 &/or MAPK3/ERK1
  • KITLG/SCF & KIT promote activation of STAT family members STAT1, STAT3 & STAT5
  • KITLG/SCF & KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol & inositol 1,4,5-trisphosphate
• KITLG/SCF acts synergistically with other cytokines, probably interleukins
• a soluble form (sKITLG) is produced by proteolytic processing of isoform 1 in the extracellular domain
• soluble form exists as a cleavage product of the extracellular domain
• heterotetramer with KIT, binding two KIT molecules; thereby mediates KIT dimerization & subsequent activation by autophosphorylation

Structure

• found in two differentially glycosylated forms, LMW-SCF & HMW-SCF.
  • LMW-SCF
    • fully N-glycosylated at Asn-145
    • partially N-glycosylated at Asn-90
    • O-glycosylated at Ser-167, Thr-168 & Thr-180,
    • not glycosylated at Asn-97 or Asn-118
  • HMW-SCF
    • N-glycosylated at Asn-118, Asn-90 & Asn-145
    • O-glycosylated at Ser-167, Thr-168 & Thr-180
    • not glycosylated at Asn-97 homodimer, non-covalently linked (probable)
• belongs to the SCF family

Compartment

• isoform 1: cell membrane; single-pass type 1 membrane protein
• isoform 2:
  • cell membrane; single-pass type 1 membrane protein
  • cytoplasm, cytoskeleton
• soluble KIT ligand: secreted

Alternative splicing

named isoforms=3

Expression

acts in the early stages of hematopoiesis

Pathology

• defects in KITLG are the cause of familial progressive hyperpigmentation

Polymorphism

• genetic variations in KITLG are associated with variation in skin/hair/eye pigmentation type 7

More general terms

• cytokine

Additional terms

• c-kit protein; mast/stem cell growth factor receptor; SCFR; proto-oncogene tyrosine-protein kinase Kit; c-kit; CD117 (KIT)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4254
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4254
• OMIM: https://mirror.omim.org/entry/145250
• OMIM: https://mirror.omim.org/entry/184745
• OMIM: https://mirror.omim.org/entry/611664
• UniProt: http://www.uniprot.org/uniprot/P21583.html