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| [1.] Shg/Fragment 028 01 - Diskussion Zuletzt bearbeitet: 2014-11-01 13:43:39 Singulus | Danial 2009, Fragment, Gesichtet, KomplettPlagiat, SMWFragment, Schutzlevel sysop, Shg |
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| Untersuchte Arbeit: Seite: 28, Zeilen: 1 ff. (komplett) |
Quelle: Danial 2009 Seite(n): S55, S56, S57, Zeilen: S55:li.Sp. 5-18; S56:re.Sp. 9-33.; S57:re.Sp. 1-11 |
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| [Although signals transduced by the engagement of growth factor receptors, such as cytokines, insulin-like-growth] factor (IGF) and nerve growth factor (NGF), were long known to promote survival, the molecular mechanisms linking their survival-promoting effect to the direct inhibition of apoptosis emerged with the identification of select components of the core apoptotic machinery that are modulated by phosphorylation events downstream of survival signaling [Datta et al., 1999; Amaravadi and Thompson, 2005]. BAD's capacity to bind and neutralize its anti-apoptotic partners, BCL-2, BCL-XL and BCL-W, is inhibited on phosphorylation by survival kinases activated by trophic factors. Various kinases have been shown to phosphorylate BAD. S136 is a preferred substrate for AKT and p70S6 kinases in the PI3K signaling pathway [Datta et al., 1997; Del Peso et al., 1997; Blume-Jensen et al., 1998; Eves et al., 1998; Harada et al., 2001]. S112 and S155 harbor bona fide protein kinase A (PKA) consensus sites that can also be recognized by p90 ribosomal S6 kinase (p90RSK), a kinase activated by the MAPK pathway that shares multiple common substrates with PKA [Datta et al., 2000; Tan et al., 2000; Houslay, 2006]. Modification of BAD by p90RSK is consistent with several studies indicating that the activation of the RAS/RAF/MEK/MAPK pathway modulates BAD phosphorylation [Bonni et al., 1999; Fang et al., 1999; Scheid et al., 1999]. RAF can localize to mitochondria [Wang et al., 1996; Gotz et al., 2005], and its activated forms promote BAD phosphorylation [Fang et al., 1999]. However, RAF modulation of BAD phosphorylation is likely indirect through other kinases such as AKT [Fang et al., 1999; Wiese et al., 2001; von Gise et al., 2001; Gotz et al., 2005]. PIM kinases constitute another class of survival kinases that phosphorylate BAD predominantly on the S112 site [Fox et al., 2003; Yan et al., 2003; Macdonald et al., 2006]. The interrelationship of these phosphorylation events is especially intriguing as it suggests that BAD modification may serve as a node where distinct signaling pathways converge to regulate the core apoptotic machinery. Recent studies have proposed a sequential model of BAD dephosphorylation initiated by pS112 dephosphorylation, which may then expose pS136 and pS155 residues for dephosphorylation [Chiang et al., 2003]. Thus, both phosphorylation and dephosphorylation of BAD at the three serine sites seem to be tiered processes. Although S136 is the apical serine the phosphorylation of which is needed for neutralizing BAD's apoptotic function, pS112 dephosphorylation may be the initial dephosphorylation event required for [promoting the apoptotic activity of BAD.]
Amaravadi R, Thompson CB. (2005). The survival kinases Akt and Pim as potential pharmacological targets. J Clin Invest 115: 2618–2624. Blume-Jensen P, Janknecht R, Hunter T. (1998). The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr Biol 8: 779–782. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME. (1999). Cell survival promoted by the Ras–MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286: 1358–1362. Chiang CW, Kanies C, Kim KW, Fang WB, Parkhurst C, Xie M et al. (2003). Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. Mol Cell Biol 23: 6350–6362. Datta SR, Brunet A, Greenberg ME. (1999). Cellular survival: a play in three Akts. Genes Dev 13: 2905–2927. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231-241. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB et al. (2000). 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 6: 41–51. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. (1997). Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 24;278(5338):687-9. Eves EM, Xiong W, Bellacosa A, Kennedy SG, Tsichlis PN, Rosner MR et al. (1998). Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line. Mol Cell Biol 18: 2143–2152. Fang X, Yu S, Eder A, Mao M, Bast Jr RC, Boyd D et al. (1999). Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway. Oncogene 18: 6635–6640. Fox CJ, Hammerman PS, Cinalli RM, Master SR, Chodosh LA, Thompson CB. (2003). The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor. Genes Dev 17: 1841–1854. Gotz R, Wiese S, Takayama S, Camarero GC, Rossoll W, Schweizer U et al. (2005). Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci 8: 1169–1178. Harada H, Andersen JS, Mann M, Terada N, Korsmeyer SJ. (2001). p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci USA 98: 9666–9670. Houslay MD. (2006). A RSK(y) relationship with promiscuous PKA. Sci STKE 2006: pe32. Macdonald A, Campbell DG, Toth R, McLauchlan H, Hastie CJ, Arthur JS. (2006). Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. BMC Cell Biol 7: 1. Scheid MP, Schubert KM, Duronio V. (1999). Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase. J Biol Chem 274: 31108–31113. Tan Y, Demeter MR, Ruan H, Comb MJ. (2000). BAD Ser-155 phosphorylation regulates BAD/Bcl-XL interaction and cell survival. J Biol Chem 275: 25865–25869. von Gise A, Lorenz P, Wellbrock C, Hemmings B, Berberich-Siebelt F, Rapp UR et al. (2001). Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals. Mol Cell Biol 21: 2324–2336. Wiese S, Pei G, Karch C, Troppmair J, Holtmann B, Rapp UR et al. (2001). Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons. Nat Neurosci 4: 137–142. Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ et al. (2003). The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. J Biol Chem 278: 45358–45367. |
[Seite S55]
Although signals transduced by the engagement of growth factor receptors, such as cytokines, insulin-like-growth factor (IGF) and nerve growth factor (NGF), were long known to promote survival, the molecular mechanisms linking their survival-promoting effect to the direct inhibition of apoptosis emerged with the identification of select components of the core apoptotic machinery that are modulated by phosphorylation events downstream of survival signaling (Datta et al., 1999; Amaravadi and Thompson, 2005). BAD’s capacity to bind and neutralize its anti-apoptotic partners, BCL-2, BCL-XL and BCL-W, is inhibited on phosphorylation by survival kinases activated by trophic factors (Figure 2a). [Seite S56] BAD kinases Depending on the cellular context, various kinases have been shown to phosphorylate BAD (Figure 3). S136 is a preferred substrate for AKT and p70S6 kinases in the PI3K signaling pathway (Datta et al., 1997; del Peso et al., 1997; Blume-Jensen et al., 1998; Eves et al., 1998; Harada et al., 2001). S112 and S155 harbor bona fide protein kinase A (PKA) consensus sites that can also be recognized by p90 ribosomal S6 kinase (p90RSK), a kinase activated by the MAPK pathway that shares multiple common substrates with PKA (Datta et al., 2000; Tan et al., 2000; Houslay, 2006). Modification of BAD by p90RSK is consistent with several studies indicating that the activation of the RAS/RAF/MEK/MAPK pathway modulates BAD phosphorylation (Bonni et al., 1999; Fang et al., 1999; Scheid et al., 1999). RAF can localize to mitochondria (Wang et al., 1996a; Gotz et al., 2005), and its activated forms promote BAD phosphorylation (Fang et al., 1999). However, RAF modulation of BAD phosphorylation is likely indirect through other kinases such as AKT (Fang et al., 1999; Wiese et al., 2001; von Gise et al., 2001; Gotz et al., 2005). PIM kinases constitute another class of survival kinases that phosphorylate BAD predominantly on the S112 site (Fox et al., 2003; Yan et al., 2003; Macdonald et al., 2006). [...] The interrelationship of these phosphorylation events is especially intriguing as it suggests that BAD modification may serve as a node where distinct signaling pathways converge to regulate the core apoptotic machinery. [Seite S57] Recent studies have proposed a sequential model of BAD dephosphorylation initiated by pS112 dephosphorylation, which may then expose pS136 and pS155 residues for dephosphorylation (Chiang et al., 2003). Thus, both phosphorylation and dephosphorylation of BAD at the three serine sites seem to be tiered processes. Although S136 is the apical serine the phosphorylation of which is needed for neutralizing BAD’s apoptotic function, pS112 dephosphorylation may be the initial dephosphorylation event required for promoting the apoptotic activity of BAD. Amaravadi R, Thompson CB. (2005). The survival kinases Akt and Pim as potential pharmacological targets. J Clin Invest 115: 2618–2624. Blume-Jensen P, Janknecht R, Hunter T. (1998). The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr Biol 8: 779–782. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME. (1999). Cell survival promoted by the Ras–MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286: 1358–1362. Chiang CW, Kanies C, Kim KW, Fang WB, Parkhurst C, Xie M et al. (2003). Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis. Mol Cell Biol 23: 6350–6362. Datta SR, Brunet A, Greenberg ME. (1999). Cellular survival: a play in three Akts. Genes Dev 13: 2905–2927. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y et al. (1997). Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91: 231–241. Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB et al. (2000). 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 6: 41–51. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. (1997). Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278: 687–689. Eves EM, Xiong W, Bellacosa A, Kennedy SG, Tsichlis PN, Rosner MR et al. (1998). Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line. Mol Cell Biol 18: 2143–2152. Fang X, Yu S, Eder A, Mao M, Bast Jr RC, Boyd D et al. (1999). Regulation of BAD phosphorylation at serine 112 by the Ras-mitogen-activated protein kinase pathway. Oncogene 18: 6635–6640. Fox CJ, Hammerman PS, Cinalli RM, Master SR, Chodosh LA, Thompson CB. (2003). The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor. Genes Dev 17: 1841–1854. Gotz R, Wiese S, Takayama S, Camarero GC, Rossoll W, Schweizer U et al. (2005). Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci 8: 1169–1178. Harada H, Andersen JS, Mann M, Terada N, Korsmeyer SJ. (2001). p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci USA 98: 9666–9670. Houslay MD. (2006). A RSK(y) relationship with promiscuous PKA. Sci STKE 2006: pe32. Macdonald A, Campbell DG, Toth R, McLauchlan H, Hastie CJ, Arthur JS. (2006). Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. BMC Cell Biol 7: 1. Scheid MP, Schubert KM, Duronio V. (1999). Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase. J Biol Chem 274: 31108–31113. Tan Y, Demeter MR, Ruan H, Comb MJ. (2000). BAD Ser-155 phosphorylation regulates BAD/Bcl-XL interaction and cell survival. J Biol Chem 275: 25865–25869. von Gise A, Lorenz P, Wellbrock C, Hemmings B, Berberich-Siebelt F, Rapp UR et al. (2001). Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals. Mol Cell Biol 21: 2324–2336. Wang HG, Rapp UR, Reed JC. (1996a). Bcl-2 targetsthe protein kinase Raf-1 to mitochondria. Cell 87: 629–638. Wiese S, Pei G, Karch C, Troppmair J, Holtmann B, Rapp UR et al. (2001). Specific function of B-Raf in mediating survival of embryonic motoneurons and sensory neurons. Nat Neurosci 4: 137–142. Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ et al. (2003). The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. J Biol Chem 278: 45358–45367. |
Sieht nach einem sorgfältigen und sehr detaillierten Literaturreferat aus - ist aber eine Kopie bis hin zur äußeren Form der Literaturverweise - ohne Hinweis auf eine Übernahme. "Gotz et al., 2005" müsste "Götz et al., 2005" sein (in beiden Texten). Der Nachweis für "Wang et al., 1996" fehlt bei Shg. |
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Letzte Bearbeitung dieser Seite: durch Benutzer:Singulus, Zeitstempel: 20141101134425