Synthesis and targeting of insulin-like growth factor-I to the hormone storage granules in an endocrine cell line.
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.
Schmidt
W K
WK
Department of Molecular and Cell Biology, University of California at Berkeley 94720-3200.
Moore
H P
HP
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
D015415:Biomarkers; D002352:Carrier Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone