Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter

Geissler, Edwin N.; Liao, Martha; Brook, David; Martin, Francis H.; Zsebo, KM; Housman, David E.; Galli, Stephen J.

doi:10.1007/bf01232978

Cited by 80 publications

(40 citation statements)

References 51 publications

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“…A single SCF gene that maps to 12q22-24 encodes two different isoforms of the protein (38,39). A longer, 248-amino acid SCF isoform contains a proteolytic cleavage site at Ala 165 that, after cleavage, results in loss of the transmembrane region and a soluble truncated protein (40,41).…”

Section: Discussionmentioning

confidence: 99%

Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

2004

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Neural stem/progenitor cell (NSPC) migration toward sites of damaged central nervous system (CNS) tissue may represent an adaptive response for the purpose of limiting and/or repairing damage. Little is known of the mechanisms responsible for this migratory response. We constructed a cDNA library of injured mouse forebrain using subtractive suppression hybridization (SSH) to identify genes that were selectively upregulated in the injured hemisphere. We demonstrate that stem cell factor (SCF) mRNA and protein are highly induced in neurons within the zone of injured brain. Additionally, the SCF receptor c-kit is expressed on NSPCs in vitro and in vivo. Finally, we demonstrate that recombinant SCF induces potent NSPC migration in vitro and in vivo through the activation of c-kit on NSPCs. These data suggest that the SCF/c-kit pathway is involved in the migration of NSPCs to sites of brain injury and that SCF may prove useful for inducing progenitor cell recruitment to specific areas of the CNS for cell-based therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

2004

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“…SCF, a cytokine that binds to the c-Kit receptor (CD117) [16], plays an important role in hematopoiesis [17,18], spermatogenesis [19], and melanogenesis [20]. It is produced by stromal cells in fetal liver and adult bone marrow as well as by other cell types and organs [21].…”

Section: Introductionmentioning

confidence: 99%

Plant-Produced Human Recombinant Erythropoietic Growth Factors Support Erythroid Differentiation In Vitro

Musiychuk

Sivalenka²,

Jaje

et al. 2013

Stem Cells and Development

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Clinically available red blood cells (RBCs) for transfusions are at high demand, but in vitro generation of RBCs from hematopoietic stem cells requires significant quantities of growth factors. Here, we describe the production of four human growth factors: erythropoietin (EPO), stem cell factor (SCF), interleukin 3 (IL-3), and insulin-like growth factor-1 (IGF-1), either as non-fused proteins or as fusions with a carrier molecule (lichenase), in plants, using a Tobacco mosaic virus vector-based transient expression system. All growth factors were purified and their identity was confirmed by western blotting and peptide mapping. The potency of these plant-produced cytokines was assessed using TF1 cell (responsive to EPO, IL-3 and SCF) or MCF-7 cell (responsive to IGF-1) proliferation assays. The biological activity estimated here for the cytokines produced in plants was slightly lower or within the range cited in commercial sources and published literature. By comparing EC 50 values of plant-produced cytokines with standards, we have demonstrated that all four plant-produced growth factors stimulated the expansion of umbilical cord blood-derived CD34 + cells and their differentiation toward erythropoietic precursors with the same potency as commercially available growth factors. To the best of our knowledge, this is the first report on the generation of all key bioactive cytokines required for the erythroid development in a cost-effective manner using a plant-based expression system.

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“…The type III class also includes platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 and Flt3 and is characterized by an extracellular component of 5 immunoglobulin-like domains, a transmembrane segment, a juxtamembrane (JM) domain and a cytoplasmic kinase domain with a 70–100 amino acid kinase insert near its center [3]. Normally, KIT is activated when bound to its ligand, the stem cell factor (SCF), which is encoded by SCF on chromosome 12q22 [4,5,6]. KIT (CD117) is notably expressed by mast cells, hematopoietic stem cells, germ cells, melanocytes and Cajal cells of the gastrointestinal tract and is therefore functionally relevant for mast cell development, hematopoiesis, gametogenesis and melanogenesis [7].…”

Section: Introductionmentioning

confidence: 99%

<i>KIT</i> and Mastocytosis

Lim¹,

Pardanani²,

Tefferi³

2008

Acta Haematol

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KIT is a receptor tyrosine kinase that is functionally relevant for hematopoiesis, mast cell development and function, gametogenesis and melanogenesis. Normal KIT signaling requires binding to stem cell factor, and PI3K-Akt is one of the putative effector pathways. In humans, germline loss-of-function KIT mutations have been associated with piebaldism – an autosomal dominant condition characterized by depigmented patches of skin and hair. Gain-of-function KIT mutations are usually acquired and have been associated with myeloid malignancies including core binding factor acute myeloid leukemia and systemic mastocytosis (SM), germ cell tumors, gastrointestinal stromal tumors and sinonasal T cell lymphomas. KITD816V is the most prevalent KIT mutation in mast cell disease and occurs in more than 90% of the cases that fulfill the World Health Organization diagnostic criteria for SM. However, its precise pathogenetic contribution is not well understood. In clinical practice, SM is considered either indolent or aggressive depending on the respective absence or presence of symptomatic target organ dysfunction aside from skin disease. In general, conventional therapy for SM is suboptimal, and efforts are under way to develop and employ small molecule drugs that target mutant KIT.

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Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter

Cited by 80 publications

References 51 publications

Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

Plant-Produced Human Recombinant Erythropoietic Growth Factors Support Erythroid Differentiation In Vitro

<i>KIT</i> and Mastocytosis

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