Biological roles for the second domain of thrombopoietin.
Thrombopoietin (TPO) has been isolated from the plasma of animals in several laboratories as several molecular species which vary in molecular weight from 19 kDa to 35 kDa. Upon biochemical analyses, all of these forms appear to represent proteolytic fragments of TPO which share the same amino-terminal sequences and are therefore truncated at their C-terminal ends. Intact recombinant TPO produced in cell culture is a 70 kDa glycoprotein which contains the full polypeptide backbone encoded by the cDNA sequence. A series of deliberate TPO truncations have been constructed by the introduction of stop codons into the cDNA at various positions. The proteins encoded by the truncated cDNAs have been purified to homogeniety for the purpose of detailed biological and biochemical comparisons of such C-terminally truncated TPO proteins with the full-length intact TPO. These comparisons serve to illuminate the possible biological role(s) of the C-terminal domain, which is so far unique in the family of hematopoietic cytokines. The C-terminal domain appears to regulate the specific activity of TPO, to regulate its circulating half-life, and to promote efficient biosynthesis and secretion of the protein.
Foster
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D
ZymoGenetics, Inc., Seattle, Washington 98102, USA.
Lok
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S
D000818:Animals; D003062:Codon; D018076:DNA, Complementary / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D017353:Gene Deletion; D006031:Glycosylation; D006801:Humans; D008024:Ligands; D051379:Mice; D016296:Mutagenesis; D009363:Neoplasm Proteins; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013926:Thrombopoietin / Q000097:blood / Q000737:chemistry*
D003062:Codon; D018076:DNA, Complementary; D008024:Ligands; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; C082218:MPL protein, human; D013926:Thrombopoietin