von Dott. Raffaele La Montagna
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| [1.] Rlm/Fragment 026 01 - Diskussion Zuletzt bearbeitet: 2014-12-01 17:24:39 Singulus | Fragment, Gesichtet, KomplettPlagiat, Rlm, SMWFragment, Schutzlevel sysop, Ward and Weigel 2009 |
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| Untersuchte Arbeit: Seite: 26, Zeilen: 1 ff. (entire page) |
Quelle: Ward and Weigel 2009 Seite(n): 7 (author manuscript), Zeilen: 22 ff. |
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| However, careful examination of these studies revealed that the original observation by Zhuo et al. was evident at only high concentrations of receptor . Wong et al. also found that at high concentrations of receptor the Ser650Ala mutant is less active than wild type . AR Ser650 phosphorylation also plays an important role in nuclear export of AR in response to stress kinase signaling (29). A recent report has shown that protein phosphatase 1 (PP1) inhibition increases phosphorylation at AR Ser650 which causes a marked increase in nuclear export of AR which is not observed for the Ser650Ala mutant(46) .
This study suggests that PP1 plays a critical role in regulating AR protein stability and nuclear localization through dephosphorylation of AR at Ser650. In addition to Ser-Pro motifs, several tyrosine phosphorylation sites are present in the NTD of AR. A number of candidate sites have been identified in AR isolated from cells overexpressing Src. Based on the overall level of tyrosine phosphorylation in AR, substituting Phe for Tyr534 reduced the Tyr phosphorylation most substantially suggesting that this is a major site under these conditions(47). 29)Daniel Gioeli, Ben E. Black, Vicki Gordon, Adam Spencer, Cristina T. Kesler, Scott T. Eblen, Bryce M. Paschal, and Michael J. Weber. Stress Kinase Signaling Regulates Androgen Receptor Phosphorylation, Transcription, and Localization Mol Endocrinol. 2006 Mar;20(3):503-15. Epub 2005 Nov 10 46) Chen, S., Kesler, C. T., Paschal, B. M., and Balk, S. P. (2009) Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1. J. Biol. Chem. 284, 25576–25584. 47) Guo, Z., Dai, B., Jiang, T., Xu, K., Xie, Y., Kim, O., Nesheiwat, I., Kong, X., Melamed, J., Handratta, V. D., Njar, V. C., Brodie, A. M., Yu, L. R., Veenstra, T. D., Chen, H., and Qiu, Y. (2006) Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell. 10, 309–319.]. |
However, careful examination of these studies revealed that the original observation by Zhuo et al was evident at only high concentrations of receptor (56). Wong et al also found that at high concentrations of receptor the Ser650Ala mutant is less active than wild type (68). AR Ser650 phosphorylation also plays an important role in nuclear export of AR in response to stress kinase signaling (69). A recent report has shown that protein phosphatase 1 (PP1) inhibition increases phosphorylation at AR Ser650 which causes a marked increase in nuclear export of AR which is not observed for the Ser650Ala mutant (70). This study suggests that PP1 plays a critical role in regulating AR protein stability and nuclear localization through dephosphorylation of AR at Ser650.
In addition to Ser-Pro motifs, several tyrosine phosphorylation sites are present in the NTD of AR. A number of candidate sites have been identified in AR isolated from cells overexpressing Src. Based on the overall level of tyrosine phosphorylation in AR, substituting Phe for Tyr534 reduced the Tyr phosphorylation most substantially suggesting that this is a major site under these conditions (71). 56. Zhou ZX, Kemppainen JA, Wilson EM. Identification of three proline-directed phosphorylation sites in the human androgen receptor. Mol Endocrinol. 1995; 9:605–615. [PubMed: 7565807] 68. Wong HY, Burghoorn JA, Van Leeuwen M, De Ruiter PE, Schippers E, Blok LJ, Li KW, Dekker HL, De Jong L, Trapman J, Grootegoed JA, Brinkmann AO. Phosphorylation of androgen receptor isoforms. Biochem J. 2004; 383:267–276. [PubMed: 15239671] 69. Gioeli D, Black BE, Gordon V, Spencer A, Kesler CT, Eblen ST, Paschal BM, Weber MJ. Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localization. Mol Endocrinol. 2006; 20:503–515. [PubMed: 16282370] 70. Chen S, Kesler CT, Paschal BM, Balk SP. Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1. J Biol Chem. 2009 71. Guo Z, Dai B, Jiang T, Xu K, Xie Y, Kim O, Nesheiwat I, Kong X, Melamed J, Handratta VD, Njar VC, Brodie AM, Yu LR, Veenstra TD, Chen H, Qiu Y. Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell. 2006; 10:309–319. [PubMed: 17045208] |
The source is not mentioned. It is noticeable that at the two places where there are references in the source but not in the dissertation there is a superfluous space |
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