Summary

Name RPS6KA1
Full Name Ribosomal protein S6 kinase alpha-1
Synonyms S6K-alpha-1, 90 kDa ribosomal protein S6 kinase 1, p90-RSK 1, p90RSK1, p90S6K, MAP kinase-activated protein kinase 1a, MAPK-activated protein kinase 1a, MAPKAP kinase 1a, MAPKAPK-1a, Ribosomal S6 kinase 1, RSK-1 | MAPKAPK1A, RSK1
Primary ID Q15418
Links - -
Type protein
Relations 85
Pathways AMPK Signaling, FLT3-ITD signaling, Inhibition of Apoptosis, MTOR Signaling
Function Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By similarity). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation YBX1 0.56
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation H3-3A 0.2
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation L1CAM 0.484
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates activity img/direct_inhibition.png phosphorylation BAD 0.404
Publications: 4 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Inhibition of Apoptosis
+ up-regulates activity img/direct-activation.png phosphorylation CREB1 0.738
Publications: 1 Organism: Homo Sapiens
Pathways:AMPK Signaling, FLT3-ITD signaling, Inhibition of Apoptosis
+ img/unknown.png phosphorylation RANBP3 0.326
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MXD1 0.32
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.508
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CIC 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TSC2 0.76
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ETV1 0.356
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation OSTF1 0.36
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FLNA 0.393
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KA1 0.705
Publications: 8 Organism: Chlorocebus Aethiops, Homo Sapiens, Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KA1 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:AMPK Signaling, FLT3-ITD signaling, Inhibition of Apoptosis, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KA1 0.2
Publications: 6 Organism: Chlorocebus Aethiops
Pathways:AMPK Signaling, FLT3-ITD signaling, Inhibition of Apoptosis, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KA1 0.613
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:AMPK Signaling, FLT3-ITD signaling, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KA1 0.748
Publications: 8 Organism: Chlorocebus Aethiops, Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6 0.608
Publications: 4 Organism: Homo Sapiens
Pathways:MTOR Signaling
+ up-regulates img/direct-activation.png phosphorylation CCT2 0.251
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation METTL1 0.329
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation DEPTOR 0.507
Publications: 3 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDC25A 0.375
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CDC25B 0.256
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation FOS 0.545
Publications: 2 Organism: Homo Sapiens,
+ down-regulates activity img/direct_inhibition.png phosphorylation EEF2K 0.529
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NR4A3 0.319
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MITF 0.419
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation EIF4B 0.546
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation STK11 0.293
Publications: 1 Organism: Homo Sapiens
Pathways:AMPK Signaling, FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R3A 0.416
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation CARHSP1 0.337
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates quantity img/direct-activation.png phosphorylation RANBP3 0.326
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SLC9A1 0.466
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPTOR 0.564
Publications: 3 Organism: Homo Sapiens
Pathways:MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation MAGI1 0.289
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation GSK3B 0.366
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, MTOR Signaling
+ up-regulates img/direct-activation.png phosphorylation WWC1 0.342
Publications: 2 Organism: Homo Sapiens
Tissue: Breast
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CDC34 0.343
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation VASP 0.462
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation SENP2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation IRS1 0.367
Publications: 1 Organism: Homo Sapiens
Tissue: Skeletal Muscle
Pathways:AMPK Signaling, MTOR Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation TSC 0.712
Publications: 1 Organism: Homo Sapiens
Pathways:AMPK Signaling, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KA1 0.2
Publications: 1 Organism: Mus Musculus
+ up-regulates img/indirect-activation.png Translational_regulation 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation mTORC1 0.472
Publications: 1 Organism: Homo Sapiens
Pathways:AMPK Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation Histone H3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png RPS6KA1 0.366
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling