MOLECULAR AND BIOCHEMICAL-CHARACTERIZATION OF THE MOUSE-BRAIN CORTICOTROPIN-RELEASING HORMONE-BINDING PROTEIN

Citation
Dn. Cortright et al., MOLECULAR AND BIOCHEMICAL-CHARACTERIZATION OF THE MOUSE-BRAIN CORTICOTROPIN-RELEASING HORMONE-BINDING PROTEIN, Molecular and cellular endocrinology, 111(2), 1995, pp. 147-157
Citations number
39
Categorie Soggetti
Endocrynology & Metabolism","Cell Biology
ISSN journal
03037207
Volume
111
Issue
2
Year of publication
1995
Pages
147 - 157
Database
ISI
SICI code
0303-7207(1995)111:2<147:MABOTM>2.0.ZU;2-M
Abstract
A 37 kDA corticotropin-releasing hormone-binding protein (CRH-BP), dis tinct from the CRH receptor, is expressed in rat anterior pituitary co rticotrophs and many regions of the brain, suggesting that CRH-BP may modulate the biological activity of CRH. In these studies a mouse brai n CRH-BP (mCRH-BP) cDNA has been isolated and characterized. The 1666 nucleotide mCRH-BP cDNA is expressed in brain and pituitary and encode s a 322 amino acid protein that is highly homologous to human and rat CRH-BPs. Recombinant mCRH-BP, expressed in cultured mammalian cells, b inds human CRH (K-d(app)= 0.56 nM and K-i(app)= 0.37 nM) and the alpha -helical (9-41) CRH antagonist (Ki(app)= 0.28 nM) with high affinity, but exhibits much weaker affinity for ovine CRH (K-i(app)= 206 nM). Re combinant mCRH-BP also blocks CRH-induced adrenocorticotropin release from AYT-20 cells. Additional biochemical characterization of the bind ing activity of mCRH-BP indicates that hRH-BP and CRH receptor utilize different molecular interactions to bind CRH.