Regulation of Channels by the Serum and Glucocorticoid-Inducible Kinase - Implications for Transport, Excitability and Cell Proliferation

Läng, Florian; Henke, Guido; Embark, Hamdy M.; Waldegger, Siegfried; Palmada, Mònica; Böhmer, Christoph; Vallon, Volker

doi:10.1159/000070248

Cited by 126 publications

(102 citation statements)

References 136 publications

(141 reference statements)

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“…Resting membrane potential is typically more depolarized in undifferentiated respect to differentiated cells (O'Grady and Lee, 2005;Pardo, 2004) and in cancer cells respect to terminally differentiated cells (Kunzelmann, 2005). Of interest, resting membrane potential and the type and amount of K þ and Ca 2 þ currents change during both cell cycle and differentiation (Blackiston et al, 2009;Sundelacruz et al, 2009) and are atypically modified in cancer cells (Becchetti, 2011;Bielanska et al, 2009;Haren et al, 2010;Lang et al, 2003;Ohkubo and Yamazaki, 2012;Ouadid-Ahidouch and Ahidouch, 2008).…”

Section: Introductionmentioning

confidence: 99%

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

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Zecchi‐Orlandini

et al. 2015

European Journal of Pharmacology

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Chemical compounds studied in this article:α-Dendrotoxin (PubChem SID: 135651983) Chromanol (PubChem CID: 92890) Iberiotoxin (PubChem CID: 16132435) Melatonin (PubChem CID: 896) Nifedipine (PubChem CID: 4485) a b s t r a c t Big efforts have been dedicated up to now to identify novel targets for cancer treatment. The peculiar biophysical profile and the atypical ionic channels activity shown by diverse types of human cancers suggest that ion channels may be possible targets in cancer therapy. Earlier studies have shown that melatonin exerts an oncostatic action on different tumors. In particular, it was shown that melatonin was able to inhibit growth/viability and proliferation, to reduce the invasiveness and metastatic properties of human estrogen-sensitive breast adenocarcinoma MCF-7 cell line cultured in growth medium, with substantial impairments of epidermal growth factor (EGF) and Notch-1-mediated signaling. The purpose of this work was to evaluate on MCF-7 cells the possible effects of melatonin on the biophysical features known to have a role in proliferation and differentiation, by using the patch-clamp technique. Our results show that in cells cultured in growth as well as in differentiation medium melatonin caused a hyperpolarization of resting membrane potential paralleled by significant changes of the inward Ca 2 þ currents (T-and L-type), outward delayed rectifier K þ currents and cell capacitance. All these effects are involved in MCF-7 growth and differentiation. These findings strongly suggest that melatonin, acting as a modulator of different voltage-dependent ion channels, might be considered a new promising tool for specifically disrupting cell viability and differentiation pathways in tumour cells with possible beneficial effects on cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Squecco

Tani

Zecchi‐Orlandini

et al. 2015

European Journal of Pharmacology

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“…They might be considered as potential markers for molecular staging and targets for development of anticancer therapeutic strategies (Smith et al, 2002). In addition, K þ channels also control cell volume to modulate cell proliferation (Rouzaire-Dubois and Dubois, 1998;Lang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer

et al. 2007

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“…Similar to protein kinase A, the kinases have been suggested to play a broad function in transport regulation (32). The GLUT1 amino acid sequence contains a potential SGK1 phosphorylation site at position 95 Ser.…”

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SGK1 Kinase Upregulates GLUT1 Activity and Plasma Membrane Expression

et al. 2006

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Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and thus glucose transport. The effect on GLUT4 but not on GLUT1 is mediated by activation of protein kinase B (PKB). The serum-and glucocorticoid-inducible kinase SGK1, a further kinase downstream of PI3 kinase, regulates several transporters by enhancing their plasma membrane abundance. GLUT1 contains a consensus site ( 95 Ser) for phosphorylation by SGK1. Thus, the present study investigated whether GLUT1 is regulated by the kinase. Tracer-flux studies in Xenopus oocytes and HEK-293 cells demonstrated that GLUT1 transport is enhanced by constitutively active S422D SGK1. The effect requires the kinase catalytical activity since the inactive mutant K127N SGK1 failed to modulate GLUT1. GLUT1 stimulation by S422D SGK1 is not due to de novo protein synthesis but rather to an increase of the transporter's abundance in the plasma membrane. Kinetic analysis revealed that SGK1 enhances maximal transport rate without altering GLUT1 substrate affinity. These observations suggest that SGK1 regulates GLUT1 and may contribute to or account for the PI3 kinasedependent but PKB-independent stimulation of GLUT1 by insulin. Diabetes 55:421-427, 2006 I nsulin stimulates glucose transport in hormoneresponsive tissues mainly by inducing the redistribution of the facilitated hexose carrier isoforms GLUT1 (SLC2A1) and GLUT4 (SLC2A4) from intracellular compartments to the plasma membrane (1-3). The cascade of signaling events involved in glucose transporter trafficking to the cell surface in response to insulin is triggered by an increase in insulin receptor tyrosine kinase activity followed by tyrosine phosphorylation of insulin receptor substrate proteins and activation of phosphatidylinositol 3-kinase (PI3 kinase). Downstream elements of PI3 kinase include the phosphoinositide-dependent kinase PDK1, which in turn phosphorylates and thus activates the serine/threonine kinase Akt/protein kinase B (PKB) (4 -6).The role of PI3 kinase in insulin-dependent and -independent stimulation of GLUT1 and GLUT4 translocation has been confirmed by several studies using pharmacological (Wortmannin and LY294002) blockade and genetic (PI3 kinase dominant-negative mutants) knockout of the kinase (7-11). The effect of PI3 kinase on GLUT4 trafficking is mediated by PKB (12,13). PKB is, however, at least in some cells, not required for the PI3 kinase-dependent trafficking of GLUT1 (12). Thus, some other PI3 kinasedependent protein kinases are presumably involved in the regulation of GLUT1.A further downstream molecule in the PI3 kinase signaling cascade is the serum-and glucocorticoid-inducible kinase SGK1. SGK1 was originally cloned as a glucocorticoid-sensitive gene from rat mammary tumor cells (14) and later as a human cell volume-regulated gene (15). SGK1 shares ϳ80% homology with its isoforms SGK2 and SGK3 (16) and ϳ60% homology with PKB (17).To become catalytically active, SGK1 requires phosphoryl...

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Regulation of Channels by the Serum and Glucocorticoid-Inducible Kinase - Implications for Transport, Excitability and Cell Proliferation

Cited by 126 publications

References 136 publications

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer

SGK1 Kinase Upregulates GLUT1 Activity and Plasma Membrane Expression

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