2009
DOI: 10.1074/mcp.m800282-mcp200
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Systematic Mapping of Posttranslational Modifications in Human Estrogen Receptor-α with Emphasis on Novel Phosphorylation Sites

Abstract: A systematic study of posttranslational modifications of the estrogen receptor isolated from the MCF-7 human breast cancer cell line is reported. Proteolysis with multiple enzymes, mass spectrometry, and tandem mass spectrometry achieved very high sequence coverage for the full-length 66-kDa endogenous protein from estradiol-treated cell cultures. Nine phosphorylated serine residues were identified, three of which were previously unreported and none of which were previously observed by mass spectrometry by any… Show more

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Cited by 67 publications
(64 citation statements)
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“…Resistance to these therapies occurs in approximately one third of patients and relapsed disease is characterized by elevated levels and activities of certain receptors implicated in so called 'cross talk' including EGFR, HER2 and IGFR [4][5][6][7][8][9]. ERa phosphorylation appears to contribute to endocrine resistance [10] by regulating its transcriptional activity and altering stability [11,12].…”
Section: Introductionmentioning
confidence: 96%
“…Resistance to these therapies occurs in approximately one third of patients and relapsed disease is characterized by elevated levels and activities of certain receptors implicated in so called 'cross talk' including EGFR, HER2 and IGFR [4][5][6][7][8][9]. ERa phosphorylation appears to contribute to endocrine resistance [10] by regulating its transcriptional activity and altering stability [11,12].…”
Section: Introductionmentioning
confidence: 96%
“…In vitro this has usually been reported as an alteration in phosphorylation status of ER following IGF-1 treatment. Although ER is subject to extensive post translational modifications [69] the growth factor mediated phosphorylation of serine residues S118 and S167 in the AF-1 domain of human ER have been the most intensively studied and there is some evidence that this route of E 2 independent activation of ER may be partly involved in the development and maintenance of tumourigenesis in breast tissue [1,70,71]. In this fashion, IGF-1 (and other GFs) may allow the escape of ER + breast tumours from anti-oestrogen therapeutic regimens [72,73].…”
Section: Igf Axis Effects On Er Functionmentioning
confidence: 99%
“…First, AF1 resides in the receptor N terminus, which is an intrinsically disordered region and for which limited structural data are available (91). Second, although the importance of phosphorylation in the regulation of this domain has been established, it is complicated by multiple sites of phosphorylation (3,47). Focus has been drawn to serine 118 (S118), since a single point mutation to alanine impairs both ligand-dependent and ligandindependent ER␣ activity (15, 20a, 42, 90).…”
mentioning
confidence: 99%