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Membrane androgen receptor activation triggers pro-apoptotic responses in vitro and in vivo and blocks migration in colon cancer

von S. G.

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[1.] Shg/Fragment 016 05 - Diskussion
Zuletzt bearbeitet: 2014-11-02 20:10:42 Hindemith
Fragment, Gesichtet, SABiosciences Androgen Signaling 2009, SMWFragment, Schutzlevel sysop, Shg, Verschleierung

Typus
Verschleierung
Bearbeiter
Graf Isolan
Gesichtet
Yes.png
Untersuchte Arbeit:
Seite: 16, Zeilen: 5-30
Quelle: SABiosciences Androgen Signaling 2009
Seite(n): 1 (Internetquelle), Zeilen: -
Nongenomic steroid activity involves the rapid induction of conventional second messenger signal transduction cascades. Nongenomic action of androgens can occur through multiple receptors. Androgens activate cAMP and PKA through membrane androgen receptor (mAR). Androgens also induce an elevation in intracellular Ca2+ through mAR to a GPCR (G-Protein Coupled Receptor) by activating an influx through nonvoltage-gated Ca2+ channels. The increasing of intracellular calcium activates signal transduction cascades, which is included PKA (Protein Kinase-A), PKC (Protein Kinase-C), and MAPKs (Mitogen-Activated Protein Kinase). They can modulate the activity of the ARs and other transcription factors. AR can also interact with the intracellular tyrosine kinase c-Src, triggering c-Src activation. One of the targets of c-Src is the adapter protein SHC (SH2 Containing Protein). It is an upstream regulator of the MAPK pathway. The activation of AR are influenced by direct phosphorylation by MAPK [Heinlein CA, Chang C. 2002]. In another side, AR phosphorylation by ERK2 is associated with enhanced AR transcriptional activity and an increased ability to recruit the coactivator ARA70.[Heinlein CA, Chang C. 2002] The SRC family of transcriptional coactivators includes SRC1, SRC3, and TIF2 (Transcription Intermediary Factor-2). They are targets of MAPK phosphorylation and result in an increased ability of these coactivators to recruit additional coactivator complexes to the DNA-bound receptor. The nongenomic, rapid stimulation of second messenger cascades by androgens may ultimately exert biological effects through modulation of the transcriptional activity of AR or other transcription factors. Those modulations may happen by direct phosphorylation of transcriptional activators or their coregulators [Michels G, Hoppe UC. 2008]. In the absence of AR’s cognate ligand the AR can also be activated. Androgen can initiate by various growth factors.

Culig Z, Klocker H, Bartsch G, Steiner H, Hobisch A. (2003). Androgen Receptors in Prostate Cancer. J Urol. Oct.170(4):1363-1369.

Heinlein CA, Chang C. (2002). The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Mol Endocrinol 16:2181–2187.

Michels G, Hoppe UC. (2008). Rapid actions of androgens. Front Neuroendocrinol. May;29(2):182-98.

Nongenomic steroid activity typically involves the rapid induction of conventional second messenger signal transduction cascades. Nongenomic action of androgens can occur through multiple receptors. Androgens can activate cAMP and PKA through the SHBG (Sex Hormone Binding Globulin)/SHBGR complex (Ref.1). Androgens also stimulate an elevation in intracellular Ca2+ through a GPCR (G-Protein Coupled Receptor) by activating an influx through nonvoltage-gated Ca2+ channels. The elevation of intracellular calcium activates signal transduction cascades, including PKA (Protein Kinase-A), PKC (Protein Kinase-C), and MAPKs (Mitogen-Activated Protein Kinase), that can modulate the activity of the ARs and other transcription factors. AR also interacts with the intracellular tyrosine kinase c-Src, triggering c-Src activation. One of the targets of c-Src is the adapter protein SHC (SH2 Containing Protein), an upstream regulator of the MAPK pathway. The activity of AR and AR coactivators are influenced by direct phosphorylation by MAPK (Ref.3). AR phosphorylation by ERK2 is associated with enhanced AR transcriptional activity and an increased ability to recruit the coactivator ARA70. The SRC family of transcriptional coactivators: SRC1, SRC3, and TIF2 (Transcription Intermediary Factor-2) are targets of MAPK phosphorylation that results in an increased ability of these coactivators to recruit additional coactivator complexes to the DNA-bound receptor. The nongenomic, rapid stimulation of second messenger cascades by androgens may ultimately exert biological effects through modulation of the transcriptional activity of AR or other transcription factors. Such modulation may occur through direct phosphorylation of transcriptional activators or their coregulators (Ref.1). The AR can also be activated in the absence of its cognate ligand, androgen by signaling pathways initiated by various growth factors.

[...]

References:

1. Heinlein CA, Chang C
The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions.
Mol Endocrinol. 2002 Oct;16(10):2181-7.

3. Culig Z, Klocker H, Bartsch G, Steiner H, Hobisch A
Androgen Receptors in Prostate Cancer.
J Urol. 2003 Oct;170(4):1363-1369.

Anmerkungen

Ohne Hinweis auf eine Übernahme.

"Culig Z, Klocker H, Bartsch G, Steiner H, Hobisch A. (2003)" wird nicht ein einziges Mal in der Dissertation von Shg erwähnt und taucht erst im Literaturverzeichnis auf.

Sichter
(Graf Isolan), Hindemith


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