Identification of cytoplasmic motifs required for short prolactin receptor internalization

被引:43
作者
Vincent, V
Goffin, V
RozakisAdcock, M
Mornon, JP
Kelly, PA
机构
[1] FAC MED NECKER ENFANTS MALAD, INSERM U344, F-75730 PARIS 15, FRANCE
[2] UNIV PARIS 06, LAB MINERAL CRISTALLOG, F-75252 PARIS 05, FRANCE
[3] UNIV PARIS 07, CNRS URA 09, F-75252 PARIS 05, FRANCE
关键词
D O I
10.1074/jbc.272.11.7062
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cloning of rat prolactin receptor (PRLR) cDNAs revealed the existence of two isoforms, termed short and long according to the length of their cytoplasmic domain, Internalization studies show, first, that PRLR internalization is hormone-dependent and, second, that ligand-receptor complexes of the short PRLR are internalized to a larger extent compared to the long form. In order to identify regions within the cytoplasmic domain of the short PRLR required for efficient internalization, serial truncations of the cytoplasmic tail were performed by inserting a stop codon in place of those encoding residues 282, 273, 262, 253, 244, or 237 (wild type short PRLR contains 291 amino acids), Our data show that two motifs, lying within residues 253-261 and 273-281, are involved in internalization. Both regions contain a consensus feature identified within other receptors as internalization signals, namely a di-leucine peptide (amino acids 259-260) and a tetrapeptide predicted to adopt a beta-turn structure (amino acids 276-279). We propose these two motifs are involved in PRLR endocytosis, Finally, we show that alpha-adaptin, a component of adaptor protein AP-2, coprecipitates with short PRLR complexes upon PRL stimulation, which strongly suggests that PRLR internalization is mediated by the clathrin-coated pits endocytotic pathway.
引用
收藏
页码:7062 / 7068
页数:7
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