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 (STR-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 m 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.