Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor
Autore:
Wojcik, R; Berg, MA; Esposito, N; Geffner, ME; Sakati, N; Reiter, EO; Dower, S; Francke, U; Postel-Vinay, MC; Finidori, J;
Indirizzi:
Fac Med Necker Enfants Malad, INSERM, U344, F-75730 Paris 15, France Fac Med Necker Enfants Malad Paris France 15 4, F-75730 Paris 15, France Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 r, Dept Genet, Stanford, CA 94305 USA Stanford Univ, Med Ctr, Howard Hughes Med Inst, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 ghes Med Inst, Stanford, CA 94305 USA UnivUSAlif Los Angeles, Childrens Hosp, Dept Pediat, Los Angeles, CA 90095Univ Calif Los Angeles Los Angeles CA USA 90095 at, Los Angeles, CA 90095 Kingbiaisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Ara King Faisal Specialist Hosp & Res Ctr Riyadh Saudi Arabia 11211 audi Ara Baystate Med Ctr, Childrens Hosp, Dept Pediat, Springfield, MA 01199 USA Baystate Med Ctr Springfield MA USA 01199 diat, Springfield, MA 01199 USA Univfieldfield, Royal Hallamshire Hosp, Sch Med, Dept Mol & Genet Med, Shef Univ Sheffield Sheffield S Yorkshire England S10 2JF ol & Genet Med, Shef
Titolo Testata:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
fascicolo: 12, volume: 83, anno: 1998,
pagine: 4481 - 4489
SICI:
0021-972X(199812)83:12<4481:FCAASI>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXTRACELLULAR DOMAIN; INSENSITIVITY SYNDROME; GH INSENSITIVITY; GENE-MUTATIONS; SHORT STATURE; III MODULES; DWARFISM; PROTEIN; FAMILY; SUPERFAMILY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Finidori, J FacsMed Necker Enfants Malad, INSERM, U344, 156 Rue Vaugirard,F-75730 Pari Fac Med Necker Enfants Malad 156 Rue Vaugirard Paris France 15
Citazione:
R. Wojcik et al., "Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor", J CLIN END, 83(12), 1998, pp. 4481-4489

Abstract

We have analyzed the GH receptor (GHR) gene in four individuals with Laronsyndrome, and a missense mutation was identified for each patient in the extracellular domain of the GHR (D152H, I153T, Q154P, and V155G). The D152H mutation was previously reported. We have reproduced the three novel mutations in the GHR complementary DNA and analyzed their consequences in human 293 transfected cells. In cells expressing the I153T and V155G mutants, binding of [I-125]human GH at the cell surface was very low, whereas binding tototal membrane fractions was much less affected, suggesting impaired cell surface expression. Binding assays with cells expressing the Q154P mutant revealed severe defects both at the cell surface and in total particulate membrane ti actions. Immunofluorescence experiments confirmed that cell surface expression of the three mutants was altered, and colocalization studies suggested that most of the mutant receptors are retained in the endoplasmicreticulum. Endoglycosidase H resistance tests also indicated that the majority of I153T and V155G GHRs are trapped in the endoplasmic reticulum. Thus, mutations on contiguous amino acids of the GHR result in various defects. The I153T, Q154P, and V155G mutations mainly affect intracellular trafficking and binding affinity of the receptor, whereas the D152H mutation affects receptor expression, dimerization, and signaling.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 04:44:30