p70S6K 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. 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. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. Widely expressed. 5 alternative splicing and alternative initiation human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; Translation; p70 subfamily
Chromosomal Location of Human Ortholog: 17q23.1
Cellular Component:  cell junction; cytosol; mitochondrial outer membrane; mitochondrion; neuron projection; nucleoplasm; synapse
Molecular Function:  ATP binding; kinase activity; protein binding; protein kinase activity; protein serine/threonine/tyrosine kinase activity
Biological Process:  apoptotic process; cellular response to growth factor stimulus; G1/S transition of mitotic cell cycle; long-chain fatty acid import; negative regulation of apoptotic process; negative regulation of insulin receptor signaling pathway; peptidyl-serine phosphorylation; phosphatidylinositol-mediated signaling; positive regulation of mitotic cell cycle; positive regulation of translation; positive regulation of translational initiation; response to nutrient levels; signal transduction; TOR signaling
Reference #:  P23443 (UniProtKB)
Alt. Names/Synonyms: 70 kDa ribosomal protein S6 kinase 1; KS6B1; p70 ribosomal S6 kinase alpha; p70 S6 kinase alpha; p70 S6 kinase, alpha 1; p70 S6 kinase, alpha 2; p70 S6K-alpha; p70 S6KA; p70(S6K)-alpha; p70-alpha; p70-S6K; p70-S6K 1; P70S6K1; PS6K; Ribosomal protein S6 kinase beta-1; Ribosomal protein S6 kinase I; ribosomal protein S6 kinase, 70kDa, polypeptide 1; RPS6KB1; S6K; S6K-beta-1; S6K1; serine/threonine kinase 14 alpha; Serine/threonine-protein kinase 14A; STK14A
Gene Symbols: RPS6KB1
Molecular weight: 59,140 Da
Basal Isoelectric point: 6.21  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Angiogenesis  |  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  Mitochondrial Control of Apoptosis  |  mTOR Signaling  |  PI3K/Akt Signaling  |  Protein Kinase C Signaling  |  TGF-ß Signaling  |  Translation: eIF4E and p70S6K
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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p70S6K

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Cross-references to other databases:  cBioPortal  |  Pfam  |  RCSB PDB  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene