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.
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.
Small
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D
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
Levenstein
M
M
Kim
E
E
Carow
C
C
Amin
S
S
Rockwell
P
P
Witte
L
L
Burrow
C
C
Ratajczak
M Z
MZ
Gewirtz
A M
AM
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
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