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Characterization of the cellular action of the MSK inhibitor SB-747651A

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Characterization of the cellular action of the MSK inhibitor SB-747651A. / Naqvi, Shaista; Macdonald, Andrew; McCoy, Claire E.; Darragh, Joanne; Reith, Alastair D.; Arthur, J. Simon C.

In: Biochemical Journal, Vol. 441, 01.01.2012, p. 347-357.

Research output: Contribution to journalArticle

Harvard

Naqvi, S, Macdonald, A, McCoy, CE, Darragh, J, Reith, AD & Arthur, JSC 2012, 'Characterization of the cellular action of the MSK inhibitor SB-747651A' Biochemical Journal, vol 441, pp. 347-357., 10.1042/BJ20110970

APA

Naqvi, S., Macdonald, A., McCoy, C. E., Darragh, J., Reith, A. D., & Arthur, J. S. C. (2012). Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochemical Journal, 441, 347-357. 10.1042/BJ20110970

Vancouver

Naqvi S, Macdonald A, McCoy CE, Darragh J, Reith AD, Arthur JSC. Characterization of the cellular action of the MSK inhibitor SB-747651A. Biochemical Journal. 2012 Jan 1;441:347-357. Available from: 10.1042/BJ20110970

Author

Naqvi, Shaista; Macdonald, Andrew; McCoy, Claire E.; Darragh, Joanne; Reith, Alastair D.; Arthur, J. Simon C. / Characterization of the cellular action of the MSK inhibitor SB-747651A.

In: Biochemical Journal, Vol. 441, 01.01.2012, p. 347-357.

Research output: Contribution to journalArticle

Bibtex - Download

@article{a225558f55e64428aa2cceba4723cba9,
title = "Characterization of the cellular action of the MSK inhibitor SB-747651A",
author = "Shaista Naqvi and Andrew Macdonald and McCoy, {Claire E.} and Joanne Darragh and Reith, {Alastair D.} and Arthur, {J. Simon C.}",
year = "2012",
doi = "10.1042/BJ20110970",
volume = "441",
pages = "347--357",
journal = "Biochemical Journal",
issn = "0264-6021",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Characterization of the cellular action of the MSK inhibitor SB-747651A

A1 - Naqvi,Shaista

A1 - Macdonald,Andrew

A1 - McCoy,Claire E.

A1 - Darragh,Joanne

A1 - Reith,Alastair D.

A1 - Arthur,J. Simon C.

AU - Naqvi,Shaista

AU - Macdonald,Andrew

AU - McCoy,Claire E.

AU - Darragh,Joanne

AU - Reith,Alastair D.

AU - Arthur,J. Simon C.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - <p>MSK1 (mitogen- and stress-activated kinase 1) and MSK2 are nuclear protein kinases that regulate transcription downstream of the ERK 1/2 (extracellular-signal-regulated kinase 1/2) and p38 alpha MAPKs (mitogen-activated protein kinases) via the phosphorylation of CREB (cAMP-response-element-binding protein) and histone H3. Previous studies on the function of MSKs have used two inhibitors. H89 and Ro 31-8220, both of which have multiple off-target effects. In the present study, we report the characterization of the in vitro and cellular properties of an improved MSK1 inhibitor, SB-747651A. In vitro, SB-747651A inhibits MSK1 with an IC50 value of 11 nM. Screening of an in vitro panel of 117 protein kinases revealed that, at 1 mu M, SB-747651A inhibited four other kinases, PRK2 (double-stranded-RNA-dependent protein kinase 2), RSK1 (ribosomal S6 kinase 1), p70(S6K)) (S6K is S6 kinase) (p70(RSK)) and ROCK-II (Rho-associated protein kinase 2), with a similar potency to MSK1. In cells, SB-747651A fully inhibited MSK activity at 5-10 mu M. SB-747651A was found to inhibit the production of the anti-inflammatory cytokine IL-10 (interleukin-10) in wild-type, but not MSK1/2-knockout, macrophages following LPS (lipopolysaccharide) stimulation. Both SB-747651A and MSK1/2 knockout resulted in elevated pro-inflammatory cytokine production by macrophages in response to LPS. Comparison of the effects of SB-747651A, both in vitro and in cells, demonstrated that SB-747651A exhibited improved selectivity over H89 and Ro 31-8220 and therefore represents a useful tool to study MSK function in cells.</p>

AB - <p>MSK1 (mitogen- and stress-activated kinase 1) and MSK2 are nuclear protein kinases that regulate transcription downstream of the ERK 1/2 (extracellular-signal-regulated kinase 1/2) and p38 alpha MAPKs (mitogen-activated protein kinases) via the phosphorylation of CREB (cAMP-response-element-binding protein) and histone H3. Previous studies on the function of MSKs have used two inhibitors. H89 and Ro 31-8220, both of which have multiple off-target effects. In the present study, we report the characterization of the in vitro and cellular properties of an improved MSK1 inhibitor, SB-747651A. In vitro, SB-747651A inhibits MSK1 with an IC50 value of 11 nM. Screening of an in vitro panel of 117 protein kinases revealed that, at 1 mu M, SB-747651A inhibited four other kinases, PRK2 (double-stranded-RNA-dependent protein kinase 2), RSK1 (ribosomal S6 kinase 1), p70(S6K)) (S6K is S6 kinase) (p70(RSK)) and ROCK-II (Rho-associated protein kinase 2), with a similar potency to MSK1. In cells, SB-747651A fully inhibited MSK activity at 5-10 mu M. SB-747651A was found to inhibit the production of the anti-inflammatory cytokine IL-10 (interleukin-10) in wild-type, but not MSK1/2-knockout, macrophages following LPS (lipopolysaccharide) stimulation. Both SB-747651A and MSK1/2 knockout resulted in elevated pro-inflammatory cytokine production by macrophages in response to LPS. Comparison of the effects of SB-747651A, both in vitro and in cells, demonstrated that SB-747651A exhibited improved selectivity over H89 and Ro 31-8220 and therefore represents a useful tool to study MSK function in cells.</p>

U2 - 10.1042/BJ20110970

DO - 10.1042/BJ20110970

M1 - Article

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

VL - 441

SP - 347

EP - 357

ER -

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