RSK subfamily

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

p90RSK (ribosomal protein S6 kinase A1) Show summary »« Hide summary More detailed page

Target Id

1527

Nomenclature

ribosomal protein S6 kinase A1

Common abbreviation

p90RSK

Previous and unofficial names

Genes

RPS6KA1 (Hs), Rps6ka1 (Mm), Rps6ka1 (Rn)

Ensembl ID

ENSG00000117676 (Hs), ENSMUSG00000003644 (Mm), ENSRNOG00000042411 (Rn)

UniProtKB AC

Q15418 (Hs), P18653 (Mm), Q63531 (Rn)

EC number

2.7.11.1

Sub/family-selective inhibitors

BI-D1870 pIC₅₀ 7.5 [6]

Comment

Ribosomal S6 kinase 90 kDa serine/threonine kinases, also known as p90^rsk or MAPK-activated protein kinase-1 (MAPKAP-K1), are activated by MAP kinase -mediated phosphorylation. RSK protein kinases are also activated by phosphorylation by TORC1 [1,4] and PDK1 [3]. Substrates include ribosomal S6 protein (RPS6, P62753), GS3β (P49841) [8]) and the 5HT_2A receptor [7].

RSK2 (ribosomal protein S6 kinase A3) Show summary »« Hide summary More detailed page

Target Id

1528

Nomenclature

ribosomal protein S6 kinase A3

Common abbreviation

RSK2

Previous and unofficial names

Genes

RPS6KA3 (Hs), Rps6ka3 (Mm), Rps6ka3 (Rn)

Ensembl ID

ENSG00000177189 (Hs), ENSMUSG00000031309 (Mm), ENSRNOG00000006632 (Rn)

UniProtKB AC

P51812 (Hs), P18654 (Mm)

EC number

2.7.11.1

Sub/family-selective inhibitors

BI-D1870 pIC₅₀ 7.6 [6]

Selective inhibitors

BIX 02565 pIC₅₀ 9.0 [5]

Comment

Ribosomal S6 kinase 90 kDa serine/threonine kinases, also known as p90^rsk or MAPK-activated protein kinase-1 (MAPKAP-K1), are activated by MAP kinase -mediated phosphorylation. RSK protein kinases are also activated by phosphorylation by TORC1 [1,4] and PDK1 [3]. Substrates include ribosomal S6 protein (RPS6, P62753), GSK3β (P49841) [8] and the 5HT_2A receptor [7].

RSK3 (ribosomal protein S6 kinase A2) Show summary »« Hide summary More detailed page

Target Id

1529

Nomenclature

ribosomal protein S6 kinase A2

Common abbreviation

RSK3

Previous and unofficial names

Genes

RPS6KA2 (Hs), Rps6ka2 (Mm), Rps6ka2 (Rn)

Ensembl ID

ENSG00000071242 (Hs), ENSMUSG00000023809 (Mm), ENSRNOG00000013194 (Rn)

UniProtKB AC

Q15349 (Hs), Q9WUT3 (Mm)

EC number

2.7.11.1

Sub/family-selective inhibitors

BI-D1870 pIC₅₀ 7.7 [6]

Comment

Ribosomal S6 kinase 90 kDa serine/threonine kinases, also known as p90^rsk or MAPK-activated protein kinase-1 (MAPKAP-K1), are activated by MAP kinase -mediated phosphorylation. RSK protein kinases are also activated by phosphorylation by TORC1 [1,4] and PDK1 [3]. Substrates include ribosomal S6 protein (RPS6, P62753), GSK3β (P49841) [8] and the 5HT_2A receptor [7].

RSK4 (ribosomal protein S6 kinase A6) Show summary »« Hide summary More detailed page

Target Id

1530

Nomenclature

ribosomal protein S6 kinase A6

Common abbreviation

RSK4

Previous and unofficial names

RSKα6 | ribosomal protein S6 kinase, 90kD, polypeptide 6 | ribosomal protein S6 kinase alpha-6 | ribosomal protein S6 kinase, 90kDa, polypeptide 6

Genes

RPS6KA6 (Hs), Rps6ka6 (Mm), Rps6ka6 (Rn)

Ensembl ID

ENSG00000072133 (Hs), ENSMUSG00000025665 (Mm), ENSRNOG00000002592 (Rn)

UniProtKB AC

Q9UK32 (Hs), Q7TPS0 (Mm)

EC number

2.7.11.1

Inhibitors

AT-9283 pIC₅₀ 7.5 – 8.0 [2]

Sub/family-selective inhibitors

BI-D1870 pIC₅₀ 7.8 [6]

Comment

Ribosomal S6 kinase 90 kDa serine/threonine kinases, also known as p90^rsk or MAPK-activated protein kinase-1 (MAPKAP-K1), are activated by MAP kinase -mediated phosphorylation. RSK protein kinases are also activated by phosphorylation by TORC1 [1,4] and PDK1 [3]. Substrates include ribosomal S6 protein (RPS6, P62753), GSK3β (P49841) [8] and the 5HT_2A receptor [7].

References

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1. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K. (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell, 110 (2): 177-89. [PMID:12150926]

2. Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL et al.. (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J. Med. Chem., 52 (2): 379-88. [PMID:19143567]

3. Jensen CJ, Buch MB, Krag TO, Hemmings BA, Gammeltoft S, Frödin M. (1999) 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J. Biol. Chem., 274 (38): 27168-76. [PMID:10480933]

4. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell, 110 (2): 163-75. [PMID:12150925]

5. Kirrane TM, Boyer SJ, Burke J, Guo X, Snow RJ, Soleymanzadeh L, Swinamer A, Zhang Y, Madwed JB, Kashem M et al.. (2012) Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg. Med. Chem. Lett., 22 (1): 738-42. [PMID:22056746]

6. Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, Grauert M, Hoffmann M, Schnapp G, Steegmaier M et al.. (2007) BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem. J., 401 (1): 29-38. [PMID:17040210]

7. Strachan RT, Sheffler DJ, Willard B, Kinter M, Kiselar JG, Roth BL. (2009) Ribosomal S6 kinase 2 directly phosphorylates the 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor, thereby modulating 5-HT2A signaling. J. Biol. Chem., 284 (9): 5557-73. [PMID:19103592]

8. Sutherland C, Leighton IA, Cohen P. (1993) Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling. Biochem. J., 296 ( Pt 1): 15-9. [PMID:8250835]

How to cite this family page

Database page citation:

RSK subfamily. Accessed on 16/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=541.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Enzymes. Br J Pharmacol. 174 Suppl 1: S272-S359.