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FLASH GENE
Symbol RPS6KB1 contributors: mct - updated : 26-04-2015
HGNC name ribosomal protein S6 kinase, 70kDa, polypeptide 1
HGNC id 10436
Location 17q23.1      Physical location : 57.970.442 - 58.027.784
Synonym name
  • 70 kDa ribosomal protein S6 kinase 1
  • P70S6K1
  • S6K-beta-1
  • p70 S6 kinase alpha
  • p70 S6 kinase, alpha 1
  • p70 S6 kinase, alpha 2
  • p70 S6K-alpha
  • p70 S6KA
  • p70 ribosomal S6 kinase alpha
  • p70-S6K 1
  • ribosomal protein S6 kinase I
  • ribosomal protein S6 kinase beta-1
  • serine/threonine kinase 14 alpha
  • serine/threonine-protein kinase 14A
  • Synonym symbol(s) STK14A, PS6K, S6K, S6K1, p70(S6K)-alpha, p70-S6K, p70-alpha, p70S6K
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 57.34 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D17S1606 - D17S1290 - RPS6KB1 - D17S792 - D17S923 - qter
    Authors Monni (01)
    Physical map
    TRIM37 17q22-q23 tripartite motif-containing 37 LOC348235 17q23.2 hypothetical protein LOC348235 FLJ11029 17q23.2 hypothetical protein FLJ11029 FLJ10587 17q23.2 hypothetical protein FLJ10587 FLJ37451 17q23.2 hypothetical protein FLJ37451 LOC388403 17 similar to Yippee-like protein 2 (DiGeorge syndrome-related protein FKSG4) DHX40 17q23.2 DEAH (Asp-Glu-Ala-His) box polypeptide 40 CLTC 17q11-qter clathrin, heavy polypeptide (Hc) PRO0456 17q23.2 PRO0456 protein CGI-147 17q23.2 CGI-147 protein VMP1 17q23.2 likely ortholog of rat vacuole membrane protein 1 TUBD1 17q23.2 likely ortholog of mouse tubulin, delta 1 RPS6KB1 17q23.3 ribosomal protein S6 kinase, 70kDa, polypeptide 1 LOC51136 17q23.2 PTD016 protein LOC390805 17 similar to DEAH (Asp-Glu-Ala-His) box polypeptide 40 LOC388404 17 similar to TBC1 domain family member 3 (Rab GTPase-activating protein PRC17) (Prostate cancer gene 17 protein) (TRE17 alpha protein) LOC201201 17q23.2 hypothetical LOC201201 ABC1 17q23.2-q23.3 amplified in breast cancer 1 LOC388405 17 LOC388405 CA4 17q23 carbonic anhydrase IV USP32 17q23.3 ubiquitin specific protease 32 LOC124773 17q23.3 hypothetical protein LOC124773 LOC284166 17q23.3 similar to 60S ribosomal protein L12 APPBP2 17q23 amyloid beta precursor protein (cytoplasmic tail) binding protein 2 LOC388406 17 hypothetical gene supported by AK131012 PPM1D 17q23.1 protein phosphatase 1D magnesium-dependent, delta isoform BCAS3 17q23 breast carcinoma amplified sequence 3
    regionally located in the 17q23 amplicon,in breast cancer
    RNA
    TRANSCRIPTS type messenger
    text both polypeptides expressed from the longer mRNA utilizating different translational start sites
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 5332 70 525 - 1991 1922062
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systembreastmammary gland highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two non identical catalytic domains, respectively located in N and C terminal region
  • FRAP1-regulated inhibitory region within the C terminus with "RSPRR" sequence required for its target of FRAP1
  • conjugated PhosphoP , Acetylated
    HOMOLOGY
    interspecies ortholog to Rps6kb1, Mus musculus
    ortholog to RPS6KB1, Pan troglodytes
    ortholog to Rps6kb1, Rattus norvegicus
    Homologene
    FAMILY
  • RSK (ribosomal S6 kinase) family of serine/threonine kinases
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text
  • cell junction-synapse
  • basic FUNCTION
  • maybe playing an essential regulatory role in protein synthesis during cell proliferation
  • kinase activity leads to an increase in protein synthesis and cell proliferation
  • phosphorylates specifically ribosomal protein S6 in response to insulin or several classes of mitogens
  • important for signaling at two F-actin microdomains in cells and regulates cell migration
  • RPS6KB2 but not RPS6KB1 mediates prosurvival/chemoresistance signalling
  • involved in the regulation of F3 expression (Ming 2010)
  • promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation
  • influences healthy mammalian life-span
  • play important roles in the regulation of protein synthesis, cell growth and survival
  • in addition to phosphorylation, RPS6KB1, and RPS6KB2 are also targeted by lysine acetylation
  • can activate AKT1 via a negative feedback loop
  • RPS6KB1 and RPS6KB2, are important MTOR signaling effectors, but with a differential protein expression in human tissues
  • plays potentially an important role in the exaggerated expression of SREBF1 in the liver of obese patients
  • RPS6KB1 and MTOR regulate RAC1-driven platelet activation and aggregation
  • protein kinase that drives glycolysis in leukemia cells, as a target for counteracting glucose-dependent survival induced by BCR-ABL
  • determines the metabolic requirements for BCR-ABL survival
  • mutual positive regulation between RPS6KB1 and ARG2I in endothelial inflammation and aging
  • EEF2 and RPS6KB1 signaling pathways control protein synthesis and are inhibited during myocardial ischemia
  • ARG2, MAPK14, and RPS6KB1 form a positive circuit which regulates endothelial senescence and cardiovascular aging
  • CELLULAR PROCESS cell life, proliferation/growth
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    text
  • a key regulator of cell size and growth
  • a mitogen-activated protein kinase that plays a central role in the control of mRNA translation
  • serine/threonine kinase that mediates cell cycle progression and gene transcription
  • PATHWAY
    metabolism
    signaling signal transduction
  • PI3K/AKT1/RPS6KB1 pathway is essential for regulating BIRC5 mRNA expression
  • a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP binding
  • protein
  • neurabin (neural tissue-specific F-actin binding protein)
  • Protein phosphatase 2A, PP2A
  • cap-binding complex, CBC
  • regulatory associated protein of MTOR, complex 1
  • cell division cycle 2, CDC2
  • rapamycin (mTOR)
  • tumor necrosis factor receptor-associated factor 4, TRAF4
  • S6K1 Aly/REF-like target, SKAR
  • CoA synthase
  • human telomerase reverse transcriptase, hTERT
  • p-tau (S262 and S396/404)
  • platelet-derived growth factor receptor, PDGFR
  • protein kinase CK2
  • prefoldin chaperone C19orf2
  • ras-like without CAAX protein 1, ROC1
  • peptidylprolyl cis/trans isomerase, NIMA-interacting 1, PIN1
  • RICTOR is a direct target of the ribosomal protein S6 kinase-1 (RPS6KB1)
  • attractive target downstream of MTOR for activation of glycolysis in PTEN-deficient cell
  • is a novel substrate of PHLPP1
  • BCR-ABL potently activated RPS6KB1-dependent signaling and glycolysis
  • PTPN11 is required for leucine-induced activation of RPS6KB1 in skeletal myoblasts
  • PRKAA2 controls cardiac RPS6KB1 under normoxia and regulates EEF2 but not the MTOR-RPS6KB1 pathway during ischemia
  • RPS6KB1 negatively regulates TLR-mediated signals by inhibiting MAP3K7 activity
  • RPS6KB1/2 phosphorylate EIF3A to stimulate PAIP1-EIF3A interaction and consequent translation initiation
  • MTOR activation inhibits eukaryotic translation initiation factor 4E-binding protein (EIF4EBP1) and activates ribosomal protein S6 kinase 1 (RPS6KB1), both of which stimulate translation
  • cell & other
  • actin cytoskeleton
  • REGULATION
    activated by serine/threonine phosphorylation and protein kinase C
    MTOR (MTOR phosphorylation activates the protein kinase activity of RPS6KB1, which in turn regulates protein translation by phosphorylating proteins that regulate translation initiation)
    pyruvate dehydrogenase kinase, isoenzyme 1, PDK1
    inhibited by type 2A phosphatase
    Other PIN1 enhances its phosphorylation and thus amplifies insulin signaling in hepatocarcinoma cells (Lee 2009)
    regulated BY phosphoinositide 3-kinases, PI3K
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    contributes at least in part to the pathogenesis of obesity-induced hepatic steatosis and hypertriglyceridemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    PF-4708671, a novel and highly specific inhibitor of RPS6K1B proposed as a strategy for the treatment of insulin resistance
    cancer  
    PF-4708671, a novel and highly specific inhibitor of RPS6K1B proposed as a strategy for the treatment of cancer
    metabolismlipid 
    agents that specifically inhibit hepatic S6K1 activity might be potential drugs for the treatment of hypertriglyceridemia as well as hepatic steatosis
    ANIMAL & CELL MODELS
  • homozygous disruption of the Rps6kb1 gene does not affect viability or fertility of mice, but that it has a significant effect on animal growth, especially during embryogenesis
  • S6K1(-/-) mice are significantly smaller and S6K1(-/-)/S6K2(-/-) mice show a sharp reduction in viability due to perinatal lethality
  • mice deficient for S6 Kinase 1 are hypoinsulinaemic, glucose intolerant and have reduced beta-cell mass but S6K1-deficient mice are protected against obesity owing to enhanced beta-oxidation
  • mice deleted for S6K1 have increased life span and are resistance to age-related pathologies