Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells.
Cloning of a ligand for the murine flt3/flk-2 tyrosine kinase receptor was undertaken using a soluble form of the receptor to identify a source of ligand. A murine T cell line, P7B-0.3A4, was identified that appeared to express a cell surface ligand for this receptor. A cDNA clone was isolated from an expression library prepared from these cells that was capable, when transfected into cells, of conferring binding to a soluble form of the flt3/flk-2 receptor. The cDNA for this ligand encodes a type I transmembrane protein that stimulates the proliferation of cells transfected with the flt3/flk-2 receptor. A soluble form of the ligand stimulates the proliferation of defined subpopulations of murine bone marrow and fetal liver cells as well as human bone marrow cells that are highly enriched for hematopoietic stem cells and primitive uncommitted progenitor cells.
Lyman
S D
SD
Immunex Research and Development Corporation, Seattle, Washington 98101.
James
L
L
Vanden Bos
T
T
de Vries
P
P
Brasel
K
K
Gliniak
B
B
Hollingsworth
L T
LT
Picha
K S
KS
McKenna
H J
HJ
Splett
R R
RR
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D018952:Antigens, CD34; D001483:Base Sequence; D001854:Bone Marrow Cells; D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D017077:Culture Media, Conditioned; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism; D015723:Gene Library; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D019089:Stem Cell Factor; D013601:T-Lymphocytes; D014162:Transfection; D051941:fms-Like Tyrosine Kinase 3
D015703:Antigens, CD; D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D008024:Ligands; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D016173:Macrophage Colony-Stimulating Factor; C497970:FLT3 protein, human; C497971:Flt3 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3