title: STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells.
abstract: We cloned the cDNA for stem cell tyrosine kinase 1 (STK-1), the human homolog of murine Flk-2/Flt-3, from a CD34+ hematopoietic stem cell-enriched library and investigated its expression in subsets of normal human bone marrow. The cDNA encodes a protein of 993 aa with 85% identity and 92% similarity to Flk-2/Flt-3. STK-1 is a member of the type III receptor tyrosine kinase family that includes KIT (steel factor receptor), FMS (colony-stimulating factor 1R), and platelet-derived growth factor receptor. STK-1 expression in human blood and marrow is restricted to CD34+ cells, a population greatly enriched for stem/progenitor cells. Anti-STK-1 antiserum recognizes polypeptides of 160 and 130 kDa in several STK-1-expressing cell lines and in 3T3 cells transfected with a STK-1 expression vector. Antisense oligonucleotides directed against STK-1 sequences inhibited hematopoietic colony formation, most strongly in long-term bone marrow cultures. These data suggest that STK-1 may function as a growth factor receptor on hematopoietic stem and/or progenitor cells.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: D
authors.initials: D
authors.lastname: Small
authors.forename: M
authors.initials: M
authors.lastname: Levenstein
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: Carow
authors.forename: S
authors.initials: S
authors.lastname: Amin
authors.forename: P
authors.initials: P
authors.lastname: Rockwell
authors.forename: L
authors.initials: L
authors.lastname: Witte
authors.forename: C
authors.initials: C
authors.lastname: Burrow
authors.forename: M Z
authors.initials: MZ
authors.lastname: Ratajczak
authors.forename: A M
authors.initials: AM
authors.lastname: Gewirtz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34; D001483:Base Sequence; D001853:Bone Marrow / Q000201:enzymology* / Q000276:immunology; D001854:Bone Marrow Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3