Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains.
We report the isolation from a placental library, of two cDNAs that can encode high affinity receptors for granulocyte colony-stimulating factor (G-CSF) when expressed in COS-7 cells. The cDNAs are predicted to encode integral membrane proteins of 759 and 812 amino acids in length. The predicted extracellular and membrane spanning sequences of the two clones are identical, as are the first 96 amino acids of their respective cytoplasmic regions. Different COOH termini of 34 or 87 residues are predicted for the two cDNAs, due apparently to alternate splicing. The receptor with the longer cytoplasmic domain is the closest human homologue of the murine G-CSF receptor recently described by Fukunaga et al. (Fukunaga, R., E. Ishizaka-Ikeda, Y. Seto, and S. Nagata. 1990. Cell. 61:341). A hybridization probe derived from the placental G-CSF receptor cDNA detects a approximately 3-kb transcript in RNAs isolated from placenta and a number of lymphoid and myeloid cells. The extracellular region of the G-CSF receptors is composed of four distinct types of structural domains, previously recognized in other cell surface proteins. In addition to the two domains of the HP receptor family-defining region (Patthy, L. 1990. Cell. 61:13) it incorporates one NH2-terminal Ig-like domain, and three additional repeats of fibronectin type III-like domains. The presence of both an NH2-terminal Ig-like domain and multiple membrane-proximal FN3-like domains suggests that the G-CSF receptor may be derived from an ancestral NCAM-like molecule and that the G-CSF receptor may function in some adhesion or recognition events at the cell surface in addition to the binding of G-CSF.
Larsen
A
A
Immunex Corporation, Seattle, Washington 98101.
Davis
T
T
Curtis
B M
BM
Gimpel
S
S
Sims
J E
JE
Cosman
D
D
Park
L
L
Sorensen
E
E
March
C J
CJ
Smith
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005353:Fibronectins / Q000235:genetics*; D015723:Gene Library; D005803:Genes, Immunoglobulin; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011487:Protein Conformation; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D005353:Fibronectins; D015345:Oligonucleotide Probes; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D004247:DNA