The kit receptor and its ligand, steel factor, as regulators of hemopoiesis.
Mouse strains carrying mutations at the Dominant White Spotting (W) locus or the Steel (Sl) locus are anemic and display defects in pigmentation and gametogenesis. In W mutants the anemia is due to a deficiency of hemopoietic stem cells and, in Sl mutants, to a deficiency of supporting stromal cells in the bone marrow. The W locus encodes the c-kit proto-oncogene product, a cell surface receptor with protein-tyrosine kinase activity, and the Sl locus encodes its ligand, a hemopoietic cytokine known variously as Steel factor (SLF), mast cell growth factor, stem cell factor, and Kit ligand. SLF can synergize with a number of other cytokines to stimulate growth of hemopoietic progenitors in vitro and stimulates blood cell production in vivo in animals. Here we review the biological activities of SLF, with particular emphasis on its effects on hemopoietic stem and progenitor cells. We also discuss present knowledge of the molecules involved in SLF-triggered signal transduction, and speculate on potential therapeutic applications for SLF in human disease.
Broxmeyer
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HE
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Maze
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Miyazawa
K
K
Carow
C
C
Hendrie
P C
PC
Cooper
S
S
Hangoc
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G
Vadhan-Raj
S
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Lu
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L
D000740:Anemia / Q000188:drug therapy / Q000235:genetics; D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D002454:Cell Differentiation; D002465:Cell Movement; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008544:Melanocytes / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains / Q000196:embryology / Q000235:genetics / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes; D051381:Rats; D015398:Signal Transduction; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019089:Stem Cell Factor; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit