von Dr. Diana Sandulache
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| [1.] Dsa/Fragment 030 01 - Diskussion Zuletzt bearbeitet: 2016-08-09 20:33:33 WiseWoman | Dsa, Fragment, Gesichtet, KomplettPlagiat, Lang et al 2006, SMWFragment, Schutzlevel sysop |
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| Untersuchte Arbeit: Seite: 30, Zeilen: 1ff (entire page) |
Quelle: Lang et al 2006 Seite(n): 1153, 1154, Zeilen: 1153: r.col: 47ff; 1154: l.col: 1ff |
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| [Recent evidence] suggested a role of WNK1 in the activation of SGK1 by IGF-I (Xu BE. et al., (2005) J Biol Chem). According to this evidence, IGF-I induces SGK1 activity by stimulating WNK1 phosphorylation at 58Thr, a site that is phosphorylated by protein kinase B (PKB/Akt). The PI3-kinase-dependent step in the activation of SGK1 by IGF-I was thus suggested to be the PDK1-dependent activation of PKB/Akt and the subsequent phosphorylation of WNK1 at 58Thr (Xu BE. et al., (2005) J Biol Chem). Neither the catalytic activity nor the kinase domain but the NH2 [sic] -terminal 220 residues of WNK1 are required for activation of SGK1 (Xu BE. et al., (2005) J Biol Chem). WNK1 binds SGK1 directly but does not phosphorylate it, suggesting that WNK1 serves as a scaffold protein to assemble other molecules required for maximal SGK1 activation. Its phosphorylation at 58Thr by PKB-Akt may induce binding of accessory proteins or a conformational change in SGK1 that stimulates the kinase. However, further experimental evidence is needed to elucidate how WNK1 phosphorylation promotes SGK1 activation. SGK2 and SGK3 may similarly be activated by PDK1 and PDK2/H-motif kinase. The equivalent phosphorylation sites for SGK2 and SGK3 are predicted to be at 193Thr-356Ser and 253Thr-419Ser, respectively, but this requires further investigation. The kinases are also regulated by WNK1, although to a lesser extent than SGK1 (Xu BE. et al., (2005) J Biol Chem).
Replacement of the serine at position 422 by aspartate, in the human SGK, leads to the constitutively active S422DSGK1 (Kobayashi T. et al., (1999) Biochem J), whereas replacement of lysine at position 127, within the ATP-binding region required for enzymatic activity, with asparagine leads to the inactive K127NSGK1 (Kobayashi T. et al., (1999) Biochem J). Analogous mutations in the human SGK2 and SGK3 lead to the constitutively active S356DSGK2 and S419DSGK3 and the constitutively inactive K64NSGK2 and K191NSGK3. In part through the PI3-kinase pathway, SGK1 is activated by insulin (Kobayashi T. et al., (1999) Biochem J), IGF-I (Hayashi M. et al., (2001) J Biol Chem; Kobayashi T. et al., (1999) Biochem J), hepatic growth factor (HGF) (Shelly C. et al., (2002) J Cell Sci) and follicle stimulating hormone (FSH) (Richards JS. et al., (2002) Mol Endocrinol). SGK1 can be activated by bone marrow kinase/extracellular signal-regulated kinase 5 (BK/ERK5) or by p38α. The kinases do not phosphorylate SGK1 at 256Thr but at 78Ser, which is outside the catalytic domain (Hayashi M. et al., (2001) J Biol Chem; Meng F. et al., (2005) Am J Physiol Cell Physiol). How this phosphorylation activates SGK1 is not known. SGK1 can also be activated by an increase of cytosolic Ca2+ activity, an effect presumably mediated by calmodulin - dependent protein kinase kinase (CaMKK) (Imai S. et al., (2003) Life Sci). Moreover, the small G protein Rac1 activates SGK1 via a PI3-kinaseindependent pathway (Shelly C. et al., (2002) J Cell Sci). Additional activators of SGK1 include neuronal depolarization (Kumari S. et al., (2001) Brain Res), cAMP (Kumari S. et al., (2001) Brain Res; Perrotti N. et al., (2001) J Biol Chem; Thomas CP. et al., (2004) Am J Physiol Lung Cell Mol Physiol), lithium (Kumari S. et al., (2001) Brain Res), oxidation (Kobayashi T and Cohen P., (1999) Biochem J; Prasad N. et al., (2000) Biochemistry) and adhesion to fibronectin (Shelly C. et al., (2002) J Cell Sci). Similar to SGK1, SGK2 and SGK3 are activated by oxidation, insulin, and IGF-I through a signaling cascade. |
Recent evidence suggested a role of WNK1 in the activation of SGK1 by IGF-I (371). According to this evidence, IGF-I induces SGK1 activity by stimulating WNK1 phosphorylation at 58Thr, a site that is phosphorylated by protein kinase B (PKB/Akt). The PI 3-kinasedependent step in the activation of SGK1 by IGF-I was
[page 1154] thus suggested to be the PDK1-dependent activation of PKB/Akt and the subsequent phosphorylation of WNK1 at 58Thr (371). Neither the catalytic activity nor the kinase domain but the NH2-terminal 220 residues of WNK1 are required for activation of SGK1 (371). WNK1 binds SGK1 directly but does not phosphorylate it, suggesting that WNK1 serves as a scaffold protein to assemble other molecules required for maximal SGK1 activation. Its phosphorylation at 58Thr by PKB/Akt may induce binding of accessory proteins or a conformational change in SGK1 that stimulates the kinase. However, further experimental evidence is needed to elucidate how WNK1 phosphorylation promotes SGK1 activation. SGK2 and SGK3 may similarly be activated by PDK1 and PDK2/H-motif kinase. The equivalent phosphorylation sites for SGK2 and SGK3 are predicted to be at 193Thr/356Ser and 253Thr/419Ser, respectively, but this requires further investigation. The kinases are also regulated by WNK1, although to a lesser extent than SGK1 (371). Replacement of the serine at position 422 by aspartate in the human SGK1 leads to the constitutively active S422DSGK1 (172), whereas replacement of lysine at position 127, within the ATP-binding region required for enzymatic activity, with asparagine leads to the inactive K127NSGK1 (172). Analogous mutations in the human SGK2 and SGK3 lead to the constitutively active S356DSGK2 and S419DSGK3 and the constitutively inactive K64NSGK2 and K191NSGK3 (41). In part through the PI 3-kinase pathway, SGK1 is activated by insulin (171, 254), IGF-I (137, 171, 179), hepatic growth factor (HGF) (287), and follicle stimulating hormone (FSH) (265). SGK1 can be activated by bone marrow kinase/extracellular signal-regulated kinase 5 (BK/ERK5) or by p38α. The kinases do not phosphorylate SGK1 at 256Thr but at 78Ser, which is outside the catalytic domain (137, 216). How this phosphorylation activates SGK1 is not known. SGK1 can also be activated by an increase of cytosolic Ca2+ activity, an effect presumably mediated by calmodulin-dependent protein kinase kinase (CaMKK) (158). Moreover, the small G protein Rac1 activates SGK1 via a PI 3-kinase-independent pathway (287). Additional activators of SGK1 include neuronal depolarization (179), cAMP (179, 254, 315), lithium (179), oxidation (171, 256), and adhesion to fibronectin (287). Similar to SGK1, SGK2 and SGK3 are activated by oxidation, insulin, and IGF-I through a signaling cascade [page 1155] involving PI 3-kinase as well as PDK1 and PDK2/H-motif kinase (171, 335). 137. Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, and Lee JD. BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoidinducible kinase. J Biol Chem 276: 8631–8634, 2001. 158. Imai S, Okayama N, Shimizu M, and Itoh M. Increased intracellular calcium activates serum and glucocorticoid-inducible kinase 1 (SGK1) through a calmodulin-calcium calmodulin dependent kinase kinase pathway in Chinese hamster ovary cells. Life Sci 72: 2199–2209, 2003. 171. Kobayashi T and Cohen P. Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphati-dylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem J 339: 319–328, 1999. 172. Kobayashi T, Deak M, Morrice N, and Cohen P. Characterization of the structure and regulation of two novel isoforms of serum and glucocorticoid-induced protein kinase. Biochem J 344: 189–197, 1999. 179. Kumari S, Liu X, Nguyen T, Zhang X, and D’Mello SR. Distinct phosphorylation patterns underlie Akt activation by different survival factors in neurons. Brain Res 96: 157–162, 2001. 216. Meng F, Yamagiwa Y, Taffetani S, Han J, and Patel T. IL-6 activates serum and glucocorticoid kinase via p38alpha mitogenactivated protein kinase pathway. Am J Physiol Cell Physiol 289: C971–C981, 2005. 254. Perrotti N, He RA, Phillips SA, Haft CR, and Taylor SI. Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. J Biol Chem 276: 9406–9412, 2001. 256. Prasad N, Topping RS, Zhou D, and Decker SJ. Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). Biochemistry 39: 6929–6935, 2000. 265. Richards JS, Sharma SC, Falender AE, and Lo YH. Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins. Mol Endocrinol 16: 580–599, 2002. 287. Shelly C and Herrera R. Activation of SGK1 by HGF, Rac1 and integrin-mediated cell adhesion in MDCK cells: PI-3K-dependent and -independent pathways. J Cell Sci 115: 1985–1993, 2002. 315. Thomas CP, Campbell JR, Wright PJ, and Husted RF. cAMPstimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1. Am J Physiol Lung Cell Mol Physiol 287: L843–L851, 2004. 335. Virbasius JV, Song X, Pomerleau DP, Zhan Y, Zhou GW, and Czech MP. Activation of the Akt-related cytokine-independent survival kinase requires interaction of its phox domain with endosomal phosphatidylinositol 3-phosphate. Proc Natl Acad Sci USA 98: 12908–12913, 2001. 371. Xu BE, Stippec S, Lazrak A, Huang CL, and Cobb MH. WNK1 activates SGK1 by a phosphatidylinositol 3-kinase-dependent and non-catalytic mechanism. J Biol Chem 280: 34218–34223, 2005. |
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