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Author: Stephen Jones
Hematopoiesis is governed by a number of cytokines that promote the survival,
proliferation, and differentiation of hematopoietic stem cells and progenitor
cells. Stem cell factor (SCF; also known as kit ligand, mast cell growth factor,
or steel factor) is a hematopoietic cytokine that triggers its biologic effects
by binding to its receptor, c-kit. It is a glycoprotein that plays a key role in
hematopoiesis acting both as a positive and negative regulator, often in synergy
with other cytokines. The concentration of SCF in normal human serum is, on
average, 3.3 ng/mL.
SCF is a member of the helical cytokine structural superfamily characterized
by a double-crossover four-helix bundle topology. It is normally found in both
soluble and transmembrane forms. Soluble SCF exists as a non-covalently
associated homodimer is glycosylated, and has considerable secondary structure,
including regions of alpha helices and beta sheets. Each SCF monomer contains
two intra-chain disulfide bridges, Cys4-Cys89 and Cys43-Cys138. The N-terminal
141 residues of SCF have been identified as a functional core, SCF1-141, which
includes the dimer interface and portions that bind and activate the receptor
Kit. The human SCF gene has been mapped to chromosome 12q22-12q24. SCF is
produced by various fibroblast-type cells including bone marrow stromal cells.
SCF transduces signals by ligand mediated dimerization of its receptor, Kit,
which is a type III receptor protein-tyrosine kinase related to the receptors
for platelet-derived growth factor (PDGF), macrophage colony-stimulating factor,
Flt-3 ligand and vascular endothelial growth factor (VEGF). The class III
receptors are characterized by the presence of five immunoglobulin-like domains
in their extracellular portion. SCF binds to the second and third immunoglobulin
domains while the fourth domain plays a role in receptor dimerization. Binding
of SCF to Kit leads to receptor dimerization and activation of protein kinase
activity. The receptor becomes autophosphorylated at tyrosine residues during
activation; the resulting phosphotyrosine residues serve as docking sites for
signal transduction molecules containing SH2 and phosphotyrosine-binding (PTB)
domains. Activated Kit also catalyzes the phosphorylation of substrate proteins.
SCF is of particular importance in the mast cell and erythroid lineages, but
also acts on multipotential stem and progenitor cells, megakaryocytes, and a
subset of lymphoid progenitors. It also plays a key role in mast cell
development, gametogenesis, and melanogenesis. The role of SCF also includes to
change the BFU-E(burst-forming unit-erythroid) cells, which are the earliest
erythrocyte precursors in the erythrocytic series, into the CFU-E
(colony-forming unit-erythroid). SCF, along with bFGF (basic fibroblast growth
factor) and LIF (lymphocyte inhibitory factor), prevents spontaneous
differentiation of primitive embryonic stem cells in cell culture.
IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its
kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of
IMGENEX Corporation, San Diego, USA. Find out more information about Stem Cell
Factor .
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