KinaseNET

Nomenclature

Short Name:

RSK1

Full Name:

Ribosomal protein S6 kinase alpha 2

Alias:

90 kDa ribosomal protein S6 kinase 1
EC 2.7.11.1
MAPKAPK1A
P90RSK1
RPS6KA1
S6K-alpha 1
HU-1
Kinase p90RSK1
KS6A1
KS6AA

Classification

Type:

Protein-serine/threonine kinase

Group:

AGC

Family:

RSK

SubFamily:

RSK

Specific Links

BioCarta Entry:	erk pathway
Entrez-Gene Entry:	6196
Entrez-Protein Entry:	NP_066958
GeneCards Entry:	RSK1
KinBASE Entry:	RSK3
OMIM Entry:	601685
Pfam Entry:	Q15418
PhosphoNET Entry:	Q15418
Phosphosite Plus Entry:	890
Protein Data Bank Entry:	2Z7Q
ScanSite Entry:	Q15418
Source Entry:	RPS6KA1
UCSD-Nature Entry:	A002099
UniProt Entry:	Q15418
Kinexus Products:	RSK1 Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 pan-specific antibody AB-NK164-3 Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 S221 phosphosite-specific antibody AB-PK804 Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 S380 phosphosite-specific antibody AB-PK805 Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 T573 phosphosite-specific antibody AB-PK806 Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 Y220+S221 phosphosite-specific antibody AB-PK807 RPS6 (230-239) KinSub - 40S ribosomal protein S6 (K230-A239, human) peptide; RSK protein kinase substrate peptide - Powder PE-01ADP95 RPS6 (230-238) KinSub - 40S ribosomal protein S6 (K230-R238, human) peptide; p70S6K protein kinase substrate peptide - Powder PE-01ADQ95 Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (S703-L734, human) peptide - Powder PE-01AQO95 RSKSubtide - RSK1_d1 (RPS6KA2) protein kinase substrate peptide - Powder PE-01BJG90 Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (L570-Y576, human) pT573 phosphopeptide - Powder PE-04AFQ90 Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (R377-A383, human) pS380 phosphopeptide - Powder PE-04AFR99 Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (K218-G224, human) pS221 phosphopeptide - Powder PE-04AGF99 Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (K217-G224, human) pY220+pS221 phosphopeptide - Powder PE-04AHT95

General Links

Structure

Mol. Mass (Da):

82,723

# Amino Acids:

735

# mRNA Isoforms:

mRNA Isoforms:

83,932 Da (744 AA; Q15418-2); 82,723 Da (735 AA; Q15418); 81,147 Da (719 AA; Q15418-4); 72,698 Da (643 AA; Q15418-3)

4D Structure:

Forms a complex with either ERK1 or ERK2 in quiescent cells. Transiently dissociates following mitogenic stimulation.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2WNT

Subfamily Alignment

Domain Distribution:

Start	End	Domain
62	321	Pkinase
322	391	Pkinase_C
418	675	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 pan-specific antibody AB-NK164-3
○	Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 S221 phosphosite-specific antibody AB-PK804
○	Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 S380 phosphosite-specific antibody AB-PK805
○	Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 T573 phosphosite-specific antibody AB-PK806
○	Ribosomal S6 protein-serine kinase 1; Ribosomal protein S6 kinase alpha 2 Y220+S221 phosphosite-specific antibody AB-PK807
○	RPS6 (230-239) KinSub - 40S ribosomal protein S6 (K230-A239, human) peptide; RSK protein kinase substrate peptide - Powder PE-01ADP95
○	RPS6 (230-238) KinSub - 40S ribosomal protein S6 (K230-R238, human) peptide; p70S6K protein kinase substrate peptide - Powder PE-01ADQ95
○	Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (S703-L734, human) peptide - Powder PE-01AQO95
○	RSKSubtide - RSK1_d1 (RPS6KA2) protein kinase substrate peptide - Powder PE-01BJG90
○	Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (L570-Y576, human) pT573 phosphopeptide - Powder PE-04AFQ90
○	Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (R377-A383, human) pS380 phosphopeptide - Powder PE-04AFR99
○	Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (K218-G224, human) pS221 phosphopeptide - Powder PE-04AGF99
○	Ribosomal S6 protein-serine kinase 1 / Ribosomal protein S6 kinase alpha 2 (K217-G224, human) pY220+pS221 phosphopeptide - Powder PE-04AHT95

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K75.

Serine phosphorylated:

S45, S54, S72, S154-, S209+, S221+, S307, S363+, S369, S380+, S402, S637, S684, S687, S703, S732.

Threonine phosphorylated:

T225-, T359+, T384, T474, T522, T573+, T577-, T701, T733, T734.

Tyrosine phosphorylated:

Y91+, Y138, Y220+, Y228-, Y466, Y576+, Y702.

Ubiquitinated:

K66, K75, K278, K316, K500, K654.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

33

859

16

1191
3

75

10

65
1.5

38

1

0
41

1054

48

2118
30

783

14

752
4

97

41

66
20

518

19

677
100

2581

25

4531
29

759

10

683
8

197

45

145
3

82

14

74
27

705

105

667
6

147

12

33
1

25

8

24
4

101

9

92
4

93

7

41
25

647

101

3432
3

75

7

46
2

64

43

35
21

542

56

550
4

103

10

110
14

362

12

313
8

210

10

90
1.3

34

8

45
6

144

10

161
59

1522

32

2706
5

138

15

72
3

70

8

54
1.4

35

6

56
3

85

14

69
39

1005

30

710
23

591

21

671
7

191

56

303
39

1014

31

719
1.1

29

22

32

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
0

0

100
73

83.4

97
-

-

99
-

-

-
94.3

95.5

97
-

-

-
97

97.6

98.5
97.5

98.9

98
-

-

-
79.7

86.5

-
90

93.2

92
84.9

90.1

86
75.1

85.2

78
-

-

-
24.3

36.4

63
-

-

-
58.2

73

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	MAPK1 - P28482
2	TSC2 - P49815
3	MAPK3 - P27361
4	CREB1 - P16220
5	NFKBIA - P25963
6	EEF2K - O00418
7	BAD - Q92934
8	EIF4B - P23588
9	MITF - O75030
10	PPP1R3A - Q16821
11	TOB1 - P50616
12	FOS - P01100
13	ETV1 - P50549
14	FGFR1 - P11362
15	ESR1 - P03372

Regulation

Activation:

Phosphorylation at Ser-221 is required for increased phosphotransferase activity, but is insufficient by itself. Phosphorylation at Ser-363 and Ser-380 increases phosphotransferase activity. Phosphorylation at Ser-380 in Rsk2 permits recruitment and activation of PDK1 by autophosphorylation to then phosphorylate S227 (S221 in Rsk1). Phosphorylation of Thr-573 increases phosphotransferase activity.

Inhibition:

Phosphorylation at Ser-154 induces interaction with 14-3-3 and inhibits catalytic activity. Phosphorylation of Ser-732 permits dissociation of Rsk-ERK complex.

Synthesis:

Degradation:

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

RSK1	Q15418	S221	DHEKKAYSFCGTVEY	+
PDK1	O15530	S221	DHEKKAYSFCGTVEY	+
ERK1	P27361	T359	DTEFTSRTPKDSPGI	+
ERK2	P28482	T359	DTEFTSRTPKDSPGI	+
ERK2	P28482	S363	TSRTPKDSPGIPPSA	+
PKCa	P17252	S363	TSRTPKDSPGIPPSA	+
ERK1	P27361	S363	TSRTPKDSPGIPPSA	+
PDK1	O15530	S363	TSRTPKDSPGIPPSA	+
RSK1	Q15418	S380	HQLFRGFSFVATGLM	+
JNK2	P45984	S380	HQLFRGFSFVATGLM	+
JNK1	P45983	S380	HQLFRGFSFVATGLM	+
p70S6K	P23443	S380	HQLFRGFSFVATGLM	+
ERK2	P28482	T573	AENGLLMTPCYTANF	+
ERK1	P27361	T573	AENGLLMTPCYTANF	+
RSK1	Q15418	S732	RRVRKLPSTTL____

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

Bad	Q92934	S118	GRELRRMSDEFVDSF	-
Bad	Q92934	S75	EIRSRHSSYPAGTED	-
Bad	Q92934	S99	PFRGRSRSAPPNLWA	-
C-EBPb	P17676	T266	VKSKAKKTVDKHSDE
CaRHSP1	Q9Y2V2	S52	TRRTRTFSATVRASQ
CCT2	P78371	S260	GSRVRVDSTAKVAEI
CREB1	P16220	S133	EILSRRPSYRKILND	+
DAPK1	P53355	S289	QALSRKASAVNMEKF	-
DLC1	Q96QB1	S329	VTRTRSLSACNKRVG
eEF2K	O00418	S366	SPRVRTLSGSRPPLL	-
eIF4B	P23588	S406	RPRERHPSWRSEETQ
eIF4B	P23588	S409	ERHPSWRSEETQERE
eIF4B	P23588	S422	RERSRTGSESSQTGT
ERa (ESR1)	P03372	S167	GGRERLASTNDKGSM	?
ETV1 (ER81)	P50549	S191	HRFRRQLSEPCNSFP	+
ETV1 (ER81)	P50549	S216	PMYQRQMSEPNIPFP	+
ETV1 (ER81)	P50549	S334	PTYQRRGSLQLWQFL
FLNA	P21333	S2152	TRRRRAPSVANVGSH
Fos	P01100	S362	AAAHRKGSSSNEPSS	+
GMFb	P60983	T26	KFRFRKETNNAAIIM
GSK3b	P49841	S9	SGRPRTTSFAESCKP	-
H3.1	P68431	S10	TKQTARKSTGGKAPR
H3.2	P84228	S11	TKQTARKSTGGKAPR
HMGN1 (HMG14)	P05114	S6	PKRKVSSAEGAAK__
IkBa	P25963	S19	DADEWCDSGLGSLGP
IkBa	P25963	S23	WCDSGLGSLGPDAAA
IkBa	P25963	S32	LLDDRHDSGLDSMKD
IkBa	P25963	S36	RHDSGLDSMKDEEYE
Kv4.3	Q9UK17	S535	YPSTRSPSLSSHPGL
Kv4.3	Q9UK17	S569	LPATRLRSMQELSTI
LKB1 (STK11)	Q15831	S428	SSKIRRLSACKQQ__	+
Mad1 (MXD1)	Q05195	S145	IERIRMDSIGSTVSS	-
MDM2	Q00987	S166	SSRRRAISETEENSD
MDM2	Q00987	S186	RQRKRHKSDSISLSF
METTL1	Q9UBP6	S27	YYRQRAHSNPMADHT	-
MITF	O75030	S516	KTSSRRSSMSMEETE	-
N-CAM L1	P32004	S1152	RSKGGKYSVKDKEDT
NDRG2	Q9UN36	S332	LSRSRTASLTSAASV
NDRG2	Q9UN36	S350	RSRSRTLSQSSESGT
nNOS	P29475	S852	SYKVRFNSVSSYSDS
Nur77	P22736	S351	GRRGRLPSKPKQPPD	-
p27Kip1	P46527	S10	NVRVSNGSPSLERMD	-
p27Kip1	P46527	T198	PGLRRRQT_______	-
RANBP3	Q9H6Z4	S126	VKRERTSSLTQFPPS
Raptor	Q8N122	S719	PCTPRLRSVSSYGNI
Raptor	Q8N122	S721	TPRLRSVSSYGNIRA
Raptor	Q8N122	S722	PRLRSVSSYGNIRAV
RPS6	P62753	S235	IAKRRRLSSLRASTS	+
RPS6	P62753	S236	AKRRRLSSLRASTSK	+
RSK1 (RPS6KA1)	Q15418	S221	DHEKKAYSFCGTVEY	+
RSK1 (RPS6KA1)	Q15418	S380	HQLFRGFSFVATGLM	+
RSK1 (RPS6KA1)	Q15418	S732	RRVRKLPSTTL____
SLC9A1 (NHE1)	P19634	S703	MSRARIGSDPLAYEP	+
SRF	P11831	S103	RGLKRSLSEMEIGMV
TNNI3	P19429	S22	PAPIRRRSSNYRAYA
TNNI3	P19429	S23	APIRRRSSNYRAYAT
TSC2	P49815	S1798	GQRKRLISSVEDFTE
TSC2	P49815	S939	SFRARSTSLNERPKS
YBX1	P67809	S102	NPRKYLRSVGDGETV

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Experimentally derived from alignment of 63 known protein substrate phosphosites and 52 peptides phosphorylated by recombinant RSK1 in vitro tested in-house by Kinexus.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

Staurosporine	IC50 = 100 pM	5279		19397322
TTT-3002	IC50 < 2 nM
BI-D1870	IC50 < 4 nM	25023738	573107
7-hydroxystaurosporine	IC50 < 6 nM	72271	1236539
Hesperadin	Kd < 10 nM	10142586	514409	19035792
Sunitinib	Kd = 17 nM	5329102	535	18183025
JAK3 Inhibitor VI	IC50 < 25 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 < 25 nM	3813	281948	22037377
SB218078	IC50 < 25 nM	447446	289422	22037377
Lestaurtinib	Kd = 28 nM	126565		22037378
AT9283	IC50 = 37 nM	24905142
Gö6976	IC50 < 40 nM	3501	302449
Gö7874	IC50 < 40 nM	5327863
Ro-31-8220	IC50 < 40 nM	5083	6291
Ruboxistaurin	IC50 < 40 nM	153999	91829
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
Wyeth PDK1 Inhibitor Compound 1	IC50 < 40 nM
Bisindolylmaleimide I	IC50 > 50 nM	2396	7463	22037377
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
Gö6976	IC50 > 50 nM	3501	302449	22037377
IDR E804	IC50 > 50 nM	6419764	1802727	22037377
PKCb Inhibitor	IC50 > 50 nM	6419755	366266	22037377
Ro-32-0432	IC50 > 50 nM	127757	26501	22037377
SU11652	IC50 > 50 nM	24906267	13485	22037377
SureCN2579964	IC50 < 50 nM	290221	233000	22934575
Syk Inhibitor	IC50 > 50 nM	6419747	104279	22037377
BX517	IC50 < 60 nM	11161844	228654
SureCN3470757	IC50 < 60 nM	11588244	375236
A 443654	IC50 < 80 nM	10172943	379300
GSK269962A	IC50 < 80 nM	16095342	220241
Princeton's TrkA inhibitor compound 20h	IC50 < 80 nM
SB747651A	IC50 < 80 nM	11393719	188434
AT13148	IC50 = 85 nM
Amgen TBK 1 inhibitor (Compound II)	IC50 < 100 nM
AT7867	IC50 > 100 nM	11175137	428462	20423992
CHEMBL435809	IC50 = 100 nM	44352842	435809
GSK-3 Inhibitor IX	IC50 < 100 nM	5287844	409450
PF-4708671	IC50 = 100 nM
Ruxolitinib	Kd = 120 nM	25126798	1789941	22037378
Gö6983	IC50 > 150 nM	3499	261491	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
NVP-TAE684	Kd = 160 nM	16038120	509032	22037378
SB202190	Kd = 170 nM	5353940	278041	18183025
Nintedanib	Kd = 180 nM	9809715	502835	22037378
SU14813	Kd = 180 nM	10138259	1721885	18183025
SureCN2505235	IC50 < 200 nM	5353854	101797	22934575
BML-275	IC50 = 210 nM	11524144	478629	20932747
Enzastaurin	Kd = 220 nM	176167	300138	22037378
N-Benzoylstaurosporine	Kd = 240 nM	56603681	608533	19654408
AG-E-60384	IC50 > 250 nM	6419741	413188	22037377
Aloisine A	IC50 > 250 nM	5326843	75680	22037377
BCP9000906	IC50 > 250 nM	5494425	21156	22037377
Flt-3 Inhibitor II	IC50 > 250 nM	11601743	377193	22037377
Indirubin-3′-monoxime	IC50 > 250 nM	5326739		22037377
Semaxinib	IC50 > 250 nM	5329098	276711	22037377
Dovitinib	Kd = 310 nM	57336746		18183025
SB203580	Kd = 320 nM	176155	10	18183025
R547	Kd = 390 nM	6918852		22037378
GSK429286	IC50 < 400 nM	11373846	375312
KT5720	IC50 < 400 nM	3844	608532
Vandetanib	Kd = 400 nM	3081361	24828	18183025
GSK1838705A	Kd = 410 nM	25182616	464552	22037378
JNJ-7706621	Kd = 410 nM	5330790	191003	18183025
TG101348	Kd = 420 nM	16722836	1287853	22037378
IKK-2 Inhibitor IV	IC50 = 500 nM	9903786	257167	22037377
PDK1/Akt/Flt Dual Pathway Inhibitor	IC50 = 500 nM	5113385	599894	22037377
PKR Inhibitor; Negative Control	IC50 = 500 nM	16760619		22037377
SU11274	IC50 = 500 nM	9549297	261641	22037377
BX795	IC50 < 600 nM	10077147	577784
H-1152; Glycyl	IC50 < 600 nM	16760635
H-89	IC50 < 600 nM	449241	104264
R406	IC50 < 600 nM	11984591
Alvocidib	Kd = 720 nM	9910986	428690	18183025
Momelotinib	IC50 < 750 nM	25062766		19295546
AZ960	IC50 < 800 nM	25099184		18775810
Doramapimod	IC50 < 800 nM	156422	103667
GDC-0068	IC50 < 800 nM	24995523		22934575
GSK461364A	IC50 < 800 nM	15983966	1908394
HG-9-91-01	IC50 < 800 nM
MRT67307	IC50 < 800 nM	44464263
PP242	IC50 < 800 nM	25243800
Purvalanol B	IC50 < 800 nM	448991	23254
SU6656	IC50 < 800 nM	5353978	605003
Tozasertib	IC50 < 800 nM	5494449	572878
1;9-Pyrazoloanthrone	IC50 = 1 µM	8515	7064
Alsterpaullone; 2-Cyanoethyl	IC50 > 1 µM	16760286	260138	22037377
ALX-270-403-M001	IC50 > 1 µM			22037377
Aurora A Inhibitor 1 (DF)	Kd = 1 µM			21992004
Bisindolylmaleimide IV	IC50 > 1 µM	2399	266487	22037377
CI-1040	IC50 = 1 µM	6918454	105442
Compound 52	IC50 > 1 µM	2856		22037377
CZC-25146	IC50 = 1 µM
Fasudil	IC50 = 1 µM	3547	38380
GSK-3 Inhibitor X	IC50 > 1 µM	6538818	430226	22037377
GSK-3 Inhibitor XIII	IC50 > 1 µM	6419766	359482	22037377
GW 843682X	IC50 = 1 µM	9826308	514499
GW441756 hydrochloride	IC50 = 1 µM	16219400
GW5074 (Raf1 Kinase Inhibitor I)	IC50 < 1 µM	5924208
HA-1100	IC50 = 1 µM	3064778	1233300
IKK-2 Inhibitor VIII	IC50 = 1 µM	66576999	368427
IKK-3 inhibitor IX	IC50 = 1 µM	11626927	373751
MK5108	IC50 > 1 µM	24748204		20053775
MNK1 Inhibitor	IC50 = 1 µM	11644425	1240885
Novartis 12a (PKD1)	IC50 = 1 µM
NU6140	IC50 > 1 µM	10202471	1802728	22037377
Orantinib	IC50 = 1 µM	5329099	274654
Purvalanol A	IC50 = 1 µM	456214	23327
Quercetagetin	IC50 = 1 µM	5281680	413552
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN10063060	Ki > 1 µM	52936621		21391610
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
AST-487	Kd = 1.1 µM	11409972	574738	18183025
SureCN7018367	Kd < 1.25 µM	18792927	450519	19035792
GSK690693	IC50 = 1.26 µM	16725726	494089	18800763
SB431542	Kd = 1.3 µM	4521392	440084	18183025
Tofacitinib	Kd = 1.4 µM	9926791	221959	18183025
BIX02188	IC50 < 2 µM	23507698		18834865
SB415286	IC50 = 2 µM	4210951	322970
Alsterpaullone	IC50 > 3 µM	5005498	50894
KIN 112	IC50 > 3 µM
MSC 2032964A	IC50 > 3 µM
Roscovitine	Kd = 3.2 µM	160355	14762	15711537
KW2449	Kd = 3.4 µM	11427553	1908397	22037378
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
Curcumin	IC50 < 4 µM	5281767	116438
H-7	IC50 < 4 µM	3542
H-8	IC50 < 4 µM	3540	148333
JNJ-28871063	IC50 > 4 µM	17747413		17975007
BMS-690514	Kd < 4.5 µM	11349170		21531814
Caffeine	IC50 > 4.5 µM	2519	113
JNKIN7	IC50 > 4.5 µM	57340685
MLN8054	Kd = 4.8 µM	11712649	259084	22037378

Disease Linkage

General Disease Association:

Cancer, neurological disorders

Specific Diseases (Non-cancerous):

Coffin-Lowry syndrome (CLS)

Specific Cancer Types:

Tuberous sclerosis (TSC)

Comments:

RSK1 may be a tumour requiring protein (TRP). The active form of the protein kinase normally acts to promote tumour cell proliferation. Abnormal activation of RSK1 expression has been linked to many human diseases, including breast and prostate cancers. Inhibition of RSK signalling enhances the effects of enzalutamide prostate cancer therapy.

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Barrett's esophagus epithelial metaplasia (%CFC= +168, p<0.015); Cervical cancer (%CFC= -68, p<0.0001); Classical Hodgkin lymphomas (%CFC= +77, p<0.002); and Large B-cell lymphomas (%CFC= +86, p<0.0001). The COSMIC website notes an up-regulated expression score for RSK1 in diverse human cancers of 300, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 230 for this protein kinase in human cancers was 3.8-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.05 % in 24903 diverse cancer specimens. This rate is only -32 % lower than the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.41 % in 805 skin cancers tested; 0.31 % in 575 stomach cancers tested; 0.24 % in 1093 large intestine cancers tested.

Frequency of Mutated Sites:

None > 2 in 20,186 cancer specimens

Comments:

Only 4 deletions, no insertions or complex mutations.

COSMIC Entry:

RPS6KA1

OMIM Entry:

601684

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Structure

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Kinexus Products

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Binding Proteins

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