Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation

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Standard

Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation. / Allevato, G; Billestrup, N; Goujon, L; Galsgaard, E D; Norstedt, G; Postel-Vinay, M C; Kelly, P A; Nielsen, Jens Høiriis.

I: The Journal of Biological Chemistry, Bind 270, Nr. 29, 21.07.1995, s. 17210-4.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Allevato, G, Billestrup, N, Goujon, L, Galsgaard, ED, Norstedt, G, Postel-Vinay, MC, Kelly, PA & Nielsen, JH 1995, 'Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation', The Journal of Biological Chemistry, bind 270, nr. 29, s. 17210-4.

APA

Allevato, G., Billestrup, N., Goujon, L., Galsgaard, E. D., Norstedt, G., Postel-Vinay, M. C., ... Nielsen, J. H. (1995). Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation. The Journal of Biological Chemistry, 270(29), 17210-4.

Vancouver

Allevato G, Billestrup N, Goujon L, Galsgaard ED, Norstedt G, Postel-Vinay MC o.a. Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation. The Journal of Biological Chemistry. 1995 jul 21;270(29):17210-4.

Author

Allevato, G ; Billestrup, N ; Goujon, L ; Galsgaard, E D ; Norstedt, G ; Postel-Vinay, M C ; Kelly, P A ; Nielsen, Jens Høiriis. / Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation. I: The Journal of Biological Chemistry. 1995 ; Bind 270, Nr. 29. s. 17210-4.

Bibtex

@article{c3f487d35a9a439991fea58f799dc7a8,
title = "Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation",
abstract = "The functional significance of growth hormone (GH) receptor (GHR) internalization is unknown; therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptional signaling. When various mutated GHR cDNAs were transfected stably into Chinese hamster ovary cells or transiently into monkey kidney (COS-7) cells, internalization of the GHR was found to be dependent upon a domain located between amino acids 318 and 380. Mutational analysis of aromatic residues in this domain revealed that phenylalanine 346 is required for internalization. Receptor down-regulation in transiently transfected COS-7 cells was also dependent upon the phenylalanine 346 residue of the GHR, since no GH-induced down-regulation was observed in cells expressing the F346A GHR mutant. In contrast, the ability to stimulate transcription of the serine protease inhibitor 2.1 promoter by the GHR was not affected by the phenylalanine 346 to alanine mutation. These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling, suggesting that ligand-mediated endocytosis is not a prerequisite for GH-induced gene transcription.",
keywords = "Animals, Cells, Cultured, Down-Regulation, Growth Hormone, Ligands, Phenylalanine, Rats, Receptors, Somatotropin, Signal Transduction, Transcription, Genetic",
author = "G Allevato and N Billestrup and L Goujon and Galsgaard, {E D} and G Norstedt and Postel-Vinay, {M C} and Kelly, {P A} and Nielsen, {Jens H{\o}iriis}",
year = "1995",
month = "7",
day = "21",
language = "English",
volume = "270",
pages = "17210--4",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "29",

}

RIS

TY - JOUR

T1 - Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation

AU - Allevato, G

AU - Billestrup, N

AU - Goujon, L

AU - Galsgaard, E D

AU - Norstedt, G

AU - Postel-Vinay, M C

AU - Kelly, P A

AU - Nielsen, Jens Høiriis

PY - 1995/7/21

Y1 - 1995/7/21

N2 - The functional significance of growth hormone (GH) receptor (GHR) internalization is unknown; therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptional signaling. When various mutated GHR cDNAs were transfected stably into Chinese hamster ovary cells or transiently into monkey kidney (COS-7) cells, internalization of the GHR was found to be dependent upon a domain located between amino acids 318 and 380. Mutational analysis of aromatic residues in this domain revealed that phenylalanine 346 is required for internalization. Receptor down-regulation in transiently transfected COS-7 cells was also dependent upon the phenylalanine 346 residue of the GHR, since no GH-induced down-regulation was observed in cells expressing the F346A GHR mutant. In contrast, the ability to stimulate transcription of the serine protease inhibitor 2.1 promoter by the GHR was not affected by the phenylalanine 346 to alanine mutation. These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling, suggesting that ligand-mediated endocytosis is not a prerequisite for GH-induced gene transcription.

AB - The functional significance of growth hormone (GH) receptor (GHR) internalization is unknown; therefore, we have analyzed domains and individual amino acids in the cytoplasmic region of the rat GHR required for ligand-mediated receptor internalization, receptor down-regulation, and transcriptional signaling. When various mutated GHR cDNAs were transfected stably into Chinese hamster ovary cells or transiently into monkey kidney (COS-7) cells, internalization of the GHR was found to be dependent upon a domain located between amino acids 318 and 380. Mutational analysis of aromatic residues in this domain revealed that phenylalanine 346 is required for internalization. Receptor down-regulation in transiently transfected COS-7 cells was also dependent upon the phenylalanine 346 residue of the GHR, since no GH-induced down-regulation was observed in cells expressing the F346A GHR mutant. In contrast, the ability to stimulate transcription of the serine protease inhibitor 2.1 promoter by the GHR was not affected by the phenylalanine 346 to alanine mutation. These results demonstrate that phenylalanine 346 is essential for GHR internalization and down-regulation but not for transcriptional signaling, suggesting that ligand-mediated endocytosis is not a prerequisite for GH-induced gene transcription.

KW - Animals

KW - Cells, Cultured

KW - Down-Regulation

KW - Growth Hormone

KW - Ligands

KW - Phenylalanine

KW - Rats

KW - Receptors, Somatotropin

KW - Signal Transduction

KW - Transcription, Genetic

M3 - Journal article

C2 - 7615519

VL - 270

SP - 17210

EP - 17214

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -

ID: 47973183