title: Synthesis and targeting of insulin-like growth factor-I to the hormone storage granules in an endocrine cell line.
abstract: Export of growth factors is generally believed to be restricted to the constitutive secretory pathway, whereas peptide hormones are typically secreted in a regulated manner. Here we show that insulin-like growth factor (IGF)-I, a growth factor released constitutively from the liver, is synthesized and secreted from the mouse pituitary AtT-20 cell line via the regulated pathway. IGF-I production is 1500-fold less than the peptide hormone ACTH. Secretagogue induces IGF-I secretion in a manner similar to ACTH. Like ACTH, IGF-I is sorted into the regulated pathway >35-fold more efficiently than a constitutively secreted protein. Dense core granules isolated from cells transfected with a human IGF-I cDNA contain both ACTH and human IGF-I. AtT-20 cells also synthesize IGF-binding proteins, and at least one of these is secreted by the regulated pathway. Human IGF-I does not exhibit milieu-induced, concentration-dependent aggregation, in contrast to secretogranin II which sorts by a proposed aggregation mechanism. These data suggest that 1) growth factors are not solely released from tissues via the constitutive pathway, 2) IGF-I may contain information for correct granular targeting, and 3) IGF-I may be sorted by a mechanism distinct from that proposed for the secretogranins.
authors.affiliation: Department of Molecular and Cell Biology, University of California at Berkeley 94720-3200.
authors.forename: W K
authors.initials: WK
authors.lastname: Schmidt
authors.forename: H P
authors.initials: HP
authors.lastname: Moore
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone