D440N Mutation in the Acid-Labile Subunit of Insulin-Like Growth Factor Complexes Inhibits Secretion and Complex Formation

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Insulin-like growth factor-binding protein 5 complexes with the acid-labile subunit. Role of the carboxyl-terminal domain.

We have recently shown that insulin-like growth factor (IGF)-binding protein 5 forms ternary complexes with IGF-I or IGF-II and the acid-labile subunit (ALS) (Twigg, S. M., and Baxter, R. C. (1998) J. Biol. Chem. 273, 6074-6079). Because IGF-binding protein 3 (IGFBP-3) binds to ALS through its basic carboxyl-terminal domain, we tested whether a homologous region present in IGFBP-5 is involved i...

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Characterization of insulin-like growth factor-free interaction between insulin-like growth factor binding protein 3 and acid labile subunit expressed from Xenopus oocytes.

The acid-labile subunit (ALS) is known to interact with the IGF binding protein (IGFBP) in the presence of insulin-like growth factors (IGFs). Studies, however, indicate that ALS forms a doublet with IGFBP3, independent of IGFs. To characterize the structural domain required for the IGF-free ALS-IGFBP3 interaction, seven recombinant human IGFBP3 mutants were generated: three deletion mutants an...

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Deficiency of the circulating insulin-like growth factor system associated with inactivation of the acid-labile subunit gene.

From the Endocrinology Research Center, Division of Endocrinology, Ricardo Gutiérrez Children’s Hospital (H.M.D., A.S.M., M.G.R., P.P., P.S., J.J.H., H.G.J.); and the Division of Pediatrics, J.A. Fernández Hospital (S.V.B.) — both in Buenos Aires, Argentina. Address reprint requests to Mr. Domené at the Endocrinology Research Center (CEDIE), Division of Endocrinology, Ricardo Gutiérrez Children...

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BACKGROUND The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability. METHODS We undertook a prospective stud...

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ژورنال

عنوان ژورنال: Molecular Endocrinology

سال: 2011

ISSN: 0888-8809,1944-9917

DOI: 10.1210/me.2010-0295