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Determinants for desensitization and sequestration of G protein-coupled receptors often contain serine or threonine residues located in their C-ter-mini. The sequence context, however, in which these residues have to appear, and the receptor specificity of these motifs are largely unknown. Mutagenesis studies with the B2 bradykinin receptor (B2wt), stably expressed in HEK 293 cells, identified a sequence distal to N338 (NSMGTLRTSI, including I347 but not the basally phosphorylated S348) and in particular the TSI sequence therein, as a major determinant for rapid agonist-inducible internalization and the prevention of receptor hypersensitivity. . | ềFEBS Journal The role of helix 8 and of the cytosolic C-termini in the internalization and signal transduction of B1 and B2 bradykinin receptors Ạ I ova n H o f Fa I ICC not 1 A lova nd I a Raiior1 Irina alatcka a1Qtoffon Qnhi icclot 1 Cornelia RoiHI1 HicAd ici rdUooi lei - IcAai lUia DdUci I iina ix.aiaioix.aya oiciici I uUHUooici VUII Iciia uciui David Proud2 and Marianne Jochum1 1 Ludwig-Maximilians-Universitat Abteilung fur Klinische Chemie und Klinische Biochemie Munchen Germany 2 Department of Physiology Biophysics University of Calgary Alberta Canada Keywords G protein-coupled receptor helix 8 modeling internalization receptor chimera Correspondence A. Faussner Ludwig-Maximilians-Universitaet Muenchen Abt. Klinische Chemie und Klinische Biochemie Nussbaumstr. 20 D-80336 Muenchen Germany Tel 49 89 51602602 Fax 49 89 51604740 E-mail alexander.faussner@ med.uni-muenchen.de Received 21 July 2004 revised 14 September 2004 accepted 15 September 2004 doi 10.1111 j.1432-1033.2004.04390.x Determinants for desensitization and sequestration of G protein-coupled receptors often contain serine or threonine residues located in their C-ter-mini. The sequence context however in which these residues have to appear and the receptor specificity of these motifs are largely unknown. Mutagenesis studies with the B2 bradykinin receptor B2wt stably expressed in HEK 293 cells identified a sequence distal to N338 NSMGTLRTSI including I347 but not the basally phosphorylated S348 and in particular the TSI sequence therein as a major determinant for rapid agonist-inducible internalization and the prevention of receptor hypersensitivity. Chimeras of the noninternalizing B1 bradykinin receptor B1wt containing these B2wt sequences sequestered poorly however suggesting that additional motifs more proximal to N338 are required. In fact further substitution of the B1wt C-terminus with corresponding B2wt regions either at C330 7.71 following putative helix 8 B1CB2 or at the preceding Y312 .
