Hematopoietic activity of granulocyte/macrophage colony-stimulating factor is dependent upon two distinct regions of the molecule: functional analysis based upon the activities of interspecies hybrid growth factors.
Granulocyte/macrophage colony-stimulating factor (GM-CSF) is an acidic glycoprotein that stimulates hematopoiesis in vitro and in vivo. Despite a high degree of sequence homology, the GM-CSFs from human and murine sources fail to crossreact in their respective colony-forming assays. On the basis of this finding, a series of hybrid molecules containing various proportions of human- and murine-specific amino acid sequences were generated by recombinant DNA techniques and assayed for species-specific activity against human and murine marrow target cells. Two regions of GM-CSF, residues 38-48 and residues 95-111, were found to be critical for hematopoietic function. These regions are structurally characterized by an amphiphilic helix and by a disulfide-bonded loop, respectively, and are homologous in position in the human and murine growth factors. In addition, competition assays suggested that, together, these regions bind to the GM-CSF receptor.
Kaushansky
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K
Division of Hematology, University of Washington, Seattle 98195.
Shoemaker
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SG
Alfaro
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Brown
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C
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D003115:Colony-Stimulating Factors / Q000235:genetics* / Q000502:physiology; D004247:DNA / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics* / Q000502:physiology; D006410:Hematopoiesis; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D014162:Transfection
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA