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 59
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. 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. 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 preinitiation 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). 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. 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. Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1. 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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation YBX1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HIST1H3A 0.23
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation H3F3A 0.23
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CREB1 0.48
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CIC 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation HMGN1 0.14
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3A 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.42
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.42
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation RPS6KA3 0.14
Publications: 4 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.2
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ATF4 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation HMGN2 0.14
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NFATC4 0.37
Publications: 5 Organism: Mus Musculus, Homo Sapiens
Tissue: Muscle, Skeletal Muscle, Myotube
+ img/unknown.png phosphorylation TINF2 0.14
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HIST1H2BB 0.14
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
+ img/unknown.png phosphorylation NR4A1 0.31
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation KCNK3 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TH 0.2
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 0.14
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation HMGN1 0.14
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation BAD 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation WWC1 0.14
Publications: 2 Organism: Homo Sapiens
Tissue: Breast
+ up-regulates img/direct-activation.png phosphorylation EIF2AK2 0.14
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation RPS6KA3 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RPS6KA3 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition RPS6KA3 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png CENPE 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png MAD2L1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png MAD1L1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KA3 0.41
Publications: 1 Organism: Homo Sapiens