Summary

Name RPS6KB1
Full Name Ribosomal protein S6 kinase beta-1
Synonyms S6K-beta-1, S6K1, 70 kDa ribosomal protein S6 kinase 1, P70S6K1, p70-S6K 1, Ribosomal protein S6 kinase I, Serine/threonine-protein kinase 14A, p70 ribosomal S6 kinase alpha, p70 S6 kinase alpha, p70 S6K-alpha, p70 S6KA | STK14A
Primary ID P23443
Links - -
Type protein
Relations 93
Pathways FLT3-ITD signaling, Insulin Signaling, MTOR Signaling, Nucleotide Biosynthesis, Satellite: IGF1
Function Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation IRS1 0.782
Publications: 6 Organism: Mus Musculus, Homo Sapiens
Tissue: Ovary, Myotube, Brain
Pathways:Insulin Signaling, MTOR Signaling
+ down-regulates img/direct_inhibition.png phosphorylation MXD1 0.308
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation HSPB1 0.317
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ESR1 0.583
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CAD 0.385
Publications: 1 Organism: Homo Sapiens
Pathways:Nucleotide Biosynthesis
+ up-regulates img/direct-activation.png phosphorylation CAD 0.385
Publications: 1 Organism: Homo Sapiens
Pathways:Nucleotide Biosynthesis
+ up-regulates activity img/direct-activation.png phosphorylation RPS6 0.936
Publications: 2 Organism: Mus Musculus
Pathways:MTOR Signaling
+ img/unknown.png phosphorylation CCT2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TARBP2 0.332
Publications: 2 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation DEPTOR 0.661
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation EEF2K 0.726
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation URI1 0.35
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation POLDIP3 0.758
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KB1 0.392
Publications: 6 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.96
Publications: 10 Organism: Sus Scrofa, Mus Musculus, Homo Sapiens, In Vitro
Tissue: Parathyroid Hormone Secreting Cell
Pathways:FLT3-ITD signaling, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.375
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation EIF4B 0.769
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KB1 0.574
Publications: 10 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
Pathways:Nucleotide Biosynthesis
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.586
Publications: 3 Organism: Rattus Norvegicus, Homo Sapiens
Tissue: Carcinoma Cell
+ up-regulates activity img/direct-activation.png phosphorylation PFKFB2 0.251
Publications: 2 Organism: Homo Sapiens
Tissue: Heart
+ down-regulates img/direct_inhibition.png phosphorylation TP63 0.2
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SRPK2 0.368
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation IRS1 0.782
Publications: 2 Organism: Mus Musculus
Pathways:Insulin Signaling, MTOR Signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation PDPK1 0.709
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Insulin Signaling, MTOR Signaling
+ down-regulates img/direct_inhibition.png phosphorylation PDCD4 0.599
Publications: 2 Organism: Homo Sapiens
Tissue: Skin
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation TRIB2 0.362
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation GLI1 0.543
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RICTOR 0.745
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MTOR 0.96
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, MTOR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.709
Publications: 1 Organism: In Vitro
Pathways:FLT3-ITD signaling, Insulin Signaling, MTOR Signaling
+ up-regulates img/direct-activation.png phosphorylation RPS6KB1 0.709
Publications: 4 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Insulin Signaling, MTOR Signaling
+ down-regulates activity img/direct_inhibition.png dephosphorylation RPS6KB1 0.594
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.75
Publications: 2 Organism: Homo Sapiens
Pathways:Insulin Signaling
+ down-regulates activity img/direct_inhibition.png dephosphorylation RPS6KB1 0.506
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPS6KB1 0.75
Publications: 4 Organism: Homo Sapiens
Pathways:Insulin Signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MRE11 0.2
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png binding RPS6KB1 0.348
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png MAPK8 0.432
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Carcinoma Cell
+ up-regulates img/indirect-activation.png SREBF1 0.443
Publications: 1 Organism: Mus Musculus
Pathways:Insulin Signaling, MTOR Signaling
+ down-regulates img/direct_inhibition.png dephosphorylation RPS6KB1 0.708
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RPS6KB1 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Carcinoma Cell
Pathways:FLT3-ITD signaling, Insulin Signaling, MTOR Signaling, Nucleotide Biosynthesis
+ down-regulates img/indirect_inhibition.png RPS6KB1 0.8
Publications: 1 Organism: Homo Sapiens