Molecular characterization and in vitro biological activity of placentin, a new member of the insulin gene family.
Insulin and insulin-like growth factors belong to a family of polypeptides involved in essential physiological processes. Placentin, a new member of the insulin family, was recently identified as a 139-amino acid open reading frame from a cDNA clone isolated from a subtracted library of first trimester human placenta. Tris/Tricine/SDS-polyacrylamide gel electrophoresis and immunoblot analyses of histidine-tagged recombinant placentin indicate that it is composed of two peptide chains of apparent molecular masses of 4 and 13 kDa. Conditioned media produced by recombinant expression of placentin cDNA in the placental 3AsubE cell line were assayed for biological activity and found to stimulate tyrosine phosphorylation and DNA synthesis. While these effects closely mimicked those of insulin, they were not mediated by the insulin receptor as shown by the lack of tyrosine phosphorylation of this receptor upon placentin treatment. Moreover, in cytotrophoblast primary culture, production of chorionic gonadotropin, a marker of trophoblast differentiation, was increased upon treatment with placentin-conditioned media, while unaffected by insulin. These results suggest that placentin might participate in the cellular proliferation and/or differentiation processes during placental development.
Koman
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Department of Molecular Biology, Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, 82512 Martinsried, Federal Republic of Germany.
Cazaubon
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Couraud
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Ullrich
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Strosberg
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D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D017931:DNA Primers / Q000737:chemistry; D006133:Growth Substances / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000737:chemistry; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010920:Placenta / Q000502:physiology*; D011972:Receptor, Insulin / Q000378:metabolism; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D006063:Chorionic Gonadotropin; D017931:DNA Primers; D006133:Growth Substances; C101126:INSL4 protein, human; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D011972:Receptor, Insulin