Summary

Name RPS6KA3
Full Name Ribosomal protein S6 kinase alpha-3
Synonyms S6K-alpha-3, 90 kDa ribosomal protein S6 kinase 3, p90-RSK 3, p90RSK3, Insulin-stimulated protein kinase 1, ISPK-1, MAP kinase-activated protein kinase 1b, MAPK-activated protein kinase 1b, MAPKAP kinase 1b, MAPKAPK-1b, Ribosomal S6 kinase 2, RSK-2, pp90RSK2 | ISPK1, MAPKAPK1B, RSK2
Primary ID P51812
Links - -
Type protein
Relations 65
Inhibitors SL0101
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 (PubMed:9770464, PubMed:16223362, PubMed:17360704, PubMed:16213824). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:9770464, PubMed:10436156). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). 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 (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). 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 (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity).

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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 H3C1 0.2
Publications: 3 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 CREB1 0.716
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.414
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CIC 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3A 0.269
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation HMGN1 0.372
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.634
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation RPS6KA3 0.373
Publications: 4 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.713
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.2
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ATF4 0.625
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation HMGN2 0.293
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NFATC4 0.399
Publications: 5 Organism: Mus Musculus, Homo Sapiens
Tissue: Muscle, Skeletal Muscle, Myotube
+ img/unknown.png phosphorylation TINF2 0.355
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation H2BC3 0.2
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NR4A1 0.481
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation FOXN2 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation KCNK3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TH 0.273
Publications: 4 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PFKFB2 0.2
Publications: 2 Organism: Homo Sapiens
Tissue: Heart
+ img/unknown.png phosphorylation KRT18 0.304
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation HMGN1 0.372
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation BAD 0.395
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation VGLL1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation WWC1 0.2
Publications: 2 Organism: Homo Sapiens
Tissue: Breast
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CASP8 0.383
Publications: 1
+ up-regulates img/direct-activation.png phosphorylation EIF2AK2 0.2
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation RPS6KA3 0.364
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.364
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.332
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RPS6KA3 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition RPS6KA3 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation Histone H3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png CENPE 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.71
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png MAD1L1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png MAD2L1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.2
Publications: 1 Organism: Homo Sapiens