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Ribosomal ProteinsRibosomal Protein S6Protein SRibosomal Protein S6 KinasesRibosomesRibosomal Protein S6 Kinases, 70-kDaMolecular Sequence DataEscherichia coliProtein S DeficiencyBase SequenceRNA, RibosomalProtein KinasesProtein BiosynthesisAmino Acid SequenceRibosomal Protein S6 Kinases, 90-kDaAnemia, Diamond-BlackfanPhosphorylationPhosphatidylinositol 3-KinasesTOR Serine-Threonine KinasesProtein-Serine-Threonine KinasesRNA, MessengerMutationRNA, BacterialBacterial ProteinsThermus thermophilusProtein BindingMAP Kinase Signaling SystemNucleic Acid ConformationCloning, MolecularSaccharomyces cerevisiaePoly UGeobacillus stearothermophilusSequence Homology, Amino AcidBinding SitesEmetineElectrophoresis, Polyacrylamide GelTranscription, GeneticRibosome Subunits, Small, BacterialKineticsRibosome Subunits, Small, EukaryoticProtein Kinase InhibitorsSequence Homology, Nucleic AcidCell NucleolusCalcium-Calmodulin-Dependent Protein KinasesPolyribosomesGenesSirolimusSequence AlignmentPhosphoproteinsSignal TransductionOperonRibosome Subunits, Large, EukaryoticStreptomycinGenes, FungalRNA-Binding ProteinsPeptide Elongation FactorsMolecular WeightProtein Kinase CRibosome Subunits, LargeEscherichia coli ProteinsModels, MolecularGenes, BacterialParomomycinsrc-Family KinasesPeptide Chain Initiation, TranslationalRNA, Ribosomal, 16SMitogen-Activated Protein Kinase 1Protein CCell LineRNA, Ribosomal, 18SAmino AcidsCodonEnzyme ActivationElectrophoresis, Gel, Two-DimensionalEukaryotic Initiation Factor-4ESaccharomyces cerevisiae ProteinsChloroplastsRecombinant ProteinsCyclic AMP-Dependent Protein KinasesRNA, Ribosomal, 5SRibosome Subunits, SmallGene Expression RegulationComplement Inactivator ProteinsBlotting, WesternMitogen-Activated Protein Kinase 3PlasmidsPeptide Initiation FactorsProtein Structure, TertiaryCarrier ProteinsPolyenesRecombinant Fusion ProteinsRestriction MappingHalobacteriumProto-Oncogene Proteins c-aktBlotting, Northernp38 Mitogen-Activated Protein KinasesQ beta ReplicaseRNA, TransferRNA, Ribosomal, 23SDNA

Mitogen-activaSignal transductionS6K1PhosphorylationMammalianPhosphatidylinositol 3-kinaSerineAMPKPathwayPI3KMAPKIntracellularPeptidesSTK14AMeSHGenesSubstratePhosphorylatesMetabolismRegulateGenePhosphorylateP90RSKAutophagyHighly conservedCAMP RESPONSMRNAGSK3SpecificitySynthesisCatalyticSubfamiliesRegulatesMolecularInhibitsSequenceMTORC1FamilyFunctionalExpressionAntibodyCell

Mitogen-activa3

• We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. (nih.gov)
• For instance, it can be activated by oncogenic mutations of PTEN, VHL, the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. (spandidos-publications.com)
• The main IRS-1 downstream signaling pathways include type I phosphatidylinositol 3-kinase (PI3K)/Akt (PKB: protein kinase B), mammalian target of rapamycin (mTOR), and mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). (biomedcentral.com)

Signal transduction3

• In molecular biology, ribosomal s6 kinase (rsk) is a family of protein kinases involved in signal transduction. (wikipedia.org)
• By phosphorylating substrate proteins, kinases modify the activity, location and affinities of up to 30% of all cellular proteins, and direct most cellular processes, particularly in signal transduction and co-ordination of complex pathways. (wormbook.org)
• A further 91 subfamilies were found in all three metazoan kinomes, including the tyrosine kinase (TK) group and the TKL group, which mediate much of the complexity of intercellular signal transduction. (wormbook.org)

S6K13

• There are two known mammalian homologues of S6 Kinase: S6K1 and S6K2. (wikipedia.org)
• Active mTORC1 phosphorylates the eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and 40S ribosomal protein S6 kinase 1 (S6K1) to promote protein synthesis [ 3 , 4 ]. (springer.com)
• The ribosomal protein S6 kinase 1 (S6K1) is one of two mammalian p70-RSK proteins, acting as a downstream mediator of mammalian target of rapamycin (mTOR) in the phosphoinositide 3-kinase (PI3K) pathway and/or the Ras-MAPK pathway . (axonmedchem.com)

Phosphorylation7

• The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. (nih.gov)
• The phosphorylation sites identified for RSK (Ser-362) and MAP kinase (Ser-374) are in the transrepression domain. (nih.gov)
• This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling. (nih.gov)
• The p70 ribosomal S6 kinases (S6K) and p90 ribosomal S6 kinases (RSK) are distinct families of Ser/Thr kinases (EC 2.7.11.1) that regulate diverse cellular processes by phosphorylation of ribosomal protein S6 (Rps6). (axonmedchem.com)
• p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling. (axonmedchem.com)
• Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. (bvsalud.org)
• Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. (bvsalud.org)

Mammalian7

• Autophagy is either positively mediated by the adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) pathway [ 12 ], or negatively mediated by the mammalian target of rapamycin (mTOR) pathway [ 13 ]. (hindawi.com)
• Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
• 1] Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span. (axonmedchem.com)
• The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. (genetex.com)
• The mammalian target of rapamycin (mTOR) is an evolutionarily highly conserved intracellular serine/threonine kinase family member. (hindawi.com)
• ROS decreased the mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase signaling, while overexpression of IRS-1 attenuated this inhibition. (biomedcentral.com)
• When activated, AMPK phosphorylates and inhibits enzymes involved in ATP-consuming processes, such as fatty acid synthesis (e.g., acetyl-CoA carboxylase, ACC) and protein synthesis (e.g., mammalian target of rapamycin, mTOR). (alliedacademies.org)

Phosphatidylinositol 3-kina2

• ROS-mediated autophagy may occur via inhibition of IRS-1/phosphatidylinositol 3-kinase/mTOR signaling. (biomedcentral.com)
• Insulin signaling pathway activates phosphatidylinositol 3-kinase (PI3K), which phosphorylates and activates Akt (also known as protein kinase B). Akt regulates glucose transport by promoting the translocation of glucose transporters, such as GLUT4, to the plasma membrane. (alliedacademies.org)

Serine3

• Rsks are serine/threonine kinases and are activated by the MAPK/ERK pathway. (wikipedia.org)
• This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. (genetex.com)
• A family of protein serine/threonine kinases which act as intracellular signalling intermediates. (bvsalud.org)

AMPK3

• Conversely, during starvation mTORC1 is inhibited and autophagy is induced by AMP-activated protein kinase (AMPK), leading to generation of intracellular nutrients and energy during degradation of non-functional or non-essential organelles or protein aggregates [ 4 , 6 ], in turn contributing to cell survival. (springer.com)
• Herein, we showed that glibenclamide promoted insulin release and further activated autophagy through the adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) pathway in MIN-6 cells. (hindawi.com)
• AMP-Activated Protein Kinase (AMPK) is a master regulator of cellular energy status. (alliedacademies.org)

Pathway5

• Autophagy is a self-protective pathway of cell catabolism that allows cells to degrade misfolded proteins or damaged organelles, providing energy for cells and maintaining their homeostasis [ 10 , 11 ]. (hindawi.com)
• The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)
• Activated AKT phosphorylates mTOR and results in the activation of the mTORC1 signaling pathway to promote its downstream effectors, ribosomal protein S6 kinase (S6Ks), for viral protein translation. (genscript.com)
• Anti-apoptotic effects as well as pathway activities can be stimulated by an angiotensin analog (SII), which has been previously shown to activate beta-arrestin but not G protein-dependent signaling, and are abrogated by beta-arrestin-2 small interfering RNA. (duke.edu)
• Tumor cells were cultured in vitro with the proteasome inhibitor bortezomib, which stabilizes SLiPs and DRiPs, shunting proteins into the autophagy pathway [ 12 ]. (biomedcentral.com)

PI3K1

• Receptor stimulation leads to concerted activation of two pathways, ERK/p90RSK and PI3K/AKT, which converge to phosphorylate and inactivate the pro-apoptotic protein BAD. (duke.edu)

MAPK1

• There are two subfamilies of rsk, p90rsk, also known as MAPK-activated protein kinase-1 (MAPKAP-K1), and p70rsk, also known as S6-H1 Kinase or simply S6 Kinase. (wikipedia.org)

Intracellular1

• Autophagy is the "self-eating" process of degrading damaged proteins and organelles, as well as recycling intracellular energy to maintain cellular homeostasis under stress conditions. (hindawi.com)

Peptides1

• Our results establish a chemistry-based framework for engineering sustained covalent inhibition without accumulating permanently modified proteins and peptides. (rcsb.org)

STK14A1

• RPS6KB1(Ribosomal protein S6 kinase beta-1) is also named as STK14A, p70 S6KA and belongs to the S6 kinase subfamily. (ptglab.com)

MeSH1

• Ribosomal Protein S6 Kinases, 90-kDa" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uams.edu)

Genes4

• This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
• Such radiations include genes involved in spermatogenesis, chemosensation, Wnt signaling and FGF receptor-like kinases. (wormbook.org)
• Protein kinases constitute one of the largest and most important of protein families, accounting for ~2% of genes in a variety of eukaryotic genomes. (wormbook.org)
• We identified 438 protein kinase genes, including 20 atypical kinases, and an additional 25 kinase fragments or pseudogenes. (wormbook.org)

Substrate1

• The insulin receptor substrate (IRS) proteins are a family of cytoplasmic adaptor proteins recognized for their role in insulin signaling. (biomedcentral.com)

Phosphorylates2

• RSK phosphorylates a variety of proteins, including transcription factors, immediate-early gene products, translational regulators, enzymes, and structural proteins, that potentially link it to many biological processes such as cell proliferation, cell differentiation, and survival. (axonmedchem.com)
• Moreover, mTORC1 also phosphorylates eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which will result in the separation of 4EBP1 from eukaryotic translation initiation factor 4E (eIF4E) for the translation of viral proteins in shrimp. (genscript.com)

Metabolism1

• It plays a key role in cell growth and proliferation by regulating INS sensitivity, metabolism, protein synthesis, and cell cycle. (ptglab.com)

Regulate3

• Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Complex proteins 1 and 2 (TSC1/2) negatively regulate protein synthesis by inactivating the mTOR complex 1 (mTORC1) at energy limiting states. (springer.com)
• Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. (wormbook.org)
• The 90 kDa ribosomal S6 kinase (RSK) household of proteins is a gaggle of extremely conserved Ser/Thr kinases that regulate various mobile processes, resembling cell progress, cell motility, cell survival and cell proliferation. (ncbcs.org)

Gene2

• 2022. Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy. . (ncbs.res.in)
• Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)

Phosphorylate1

• Both p90 and p70 Rsk phosphorylate ribosomal protein s6, part of the translational machinery, but several other substrates have been identified, including other ribosomal proteins. (wikipedia.org)

P90RSK1

• The main distinguishing feature between p90rsk and p70rsk is that the 90 kDa family contain two non-identical kinase domains, while the 70 kDa family contain only one kinase domain. (wikipedia.org)

Autophagy2

• Experimental research found a markedly decreased expression of autophagy-related proteins such as Beclin-1, Atg12-Atg5, and LC3-II in a diabetic mouse model and in a high glucose-induced podocyte injury model [ 4 ]. (hindawi.com)
• Evidence for GO induced autophagy includes increased levels of isoform B-II microtubule-associated protein 1 light chain 3 (LC3), aggregation of green fluorescence protein-tagged LC3, and increased numbers of autophagic vacuoles in cells. (biomedcentral.com)

Highly conserved1

• Many of these pathways are highly conserved, and 53 distinct kinase functions and subfamilies appear to have been conserved between yeasts, nematodes, insects and vertebrates, with a further 91 subfamilies of kinases being seen throughout metazoan genomes. (wormbook.org)

CAMP RESPONS1

• Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN. (uams.edu)

MRNA3

• Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)
• Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. (plos.org)
• Quantitative methylation-specific PCR (QMSP), real-time reverse transcription PCR, and immunohistochemical analyses were performed to measure DNA methylation and mRNA and protein expression levels in 394 samples from Taiwanese and Korean breast cancer patients. (bvsalud.org)

GSK31

• It also stimulates glycogen synthesis by inhibiting glycogen synthase kinase 3 (GSK3) and activating glycogen synthase. (alliedacademies.org)

Specificity1

• The specificity of mAb N5-676 was confirmed by western blot analysis using unconjugated Mouse anti-S6 (pS244) antibody on lysates from untreated (lane 1) or PMA-treated (lane 2) PBMC. (bdbiosciences.com)

Synthesis1

• In the presence of nutrients, mTORC1 is activated and promotes cell growth, including protein synthesis and energy storage. (springer.com)

Catalytic2

• It mainly forms the catalytic subunits of two protein complexes, including mTOR complex 1 (mTOR complex1, mTORC1) and mTOR complex 2 (mTOR complex2, mTORC2). (hindawi.com)
• Most protein kinases share a common ePK (eukaryotic protein kinase) catalytic domain, and can be identified by sequence similarity with Blast or profile hidden Markov models (HMMs). (wormbook.org)

Subfamilies4

• Since kinases perform such a variety of distinct basic cellular functions, it is not surprising to see that 53 subfamilies and functions are present in all four kinomes ( Figure 1 ). (wormbook.org)
• The gain and loss of kinase functions and subfamilies in each evolutionary lineage is also seen. (wormbook.org)
• Distribution of 212 kinase subfamilies throughout four kinomes: the yeast Saccharomyces cerevisiae , the nematode worm Caenorhabditis elegans , the fruit fly Drosophila melanogaster and human. (wormbook.org)
• Nematodes share 153 subfamilies with human, providing close homologs for 81% (419/518) of all human kinases. (wormbook.org)

Regulates3

• The heterodimeric TSC complex negatively regulates mTORC1 activity via the GTPase activity of TSC2, towards the small G-protein RHEB (Ras homologue enriched in brain) [ 5 ]. (springer.com)
• 2017. Cytoplasmic poly (A) binding protein (PABPC2) critically regulates epidermal maintenance and turnover in planarian Schmidtea mediterranea. . (ncbs.res.in)
• 2018. FMRP Interacts with C/D Box snoRNA in the Nucleus and Regulates Ribosomal RNA Methylation. . (ncbs.res.in)

Molecular2

• A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. (uams.edu)
• RPS6KB1 is a 70 kDa protein and has 5 isoforms with the calculated molecular mass of 51-59 kDa produced by alternative initiation. (ptglab.com)

Inhibits1

• The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases. (bvsalud.org)

Sequence2

• The remaining atypical protein kinases (aPK) belong to several families, some of which have structural, but not sequence similarity to ePKs. (wormbook.org)
• The classification is based on sequence similarity within the kinase domain, the presence of additional domains, known biological functions, and conservation across divergent genomes. (wormbook.org)

MTORC11

• The phosphorylated form of 40S ribosome protein S6 is thus a marker for mTORC1 activity. (springer.com)

Family3

• The RSK family of kinases: emerging roles in cellular signaling. (axonmedchem.com)
• Kinases are deeply conserved in evolution, and the worm has family homologs for over 80% of the human kinome. (wormbook.org)
• The RSK family of kinases: emerging roles in cellular signalling. (ncbcs.org)

Functional1

• To put worm kinases into an evolutionary and functional context, we compared them with the distant kinomes of human, fly, and yeast. (wormbook.org)

Expression2

• In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
• TMEM240 protein expression was observed in normal breast tissues but was not detected in 88.2% (67/76) of breast tumors and in 90.0% (9/10) of metastatic tumors from breast cancer patients. (bvsalud.org)

Antibody1

• p70 S6K (phospho Thr421/Ser424) antibody [HL5] detects p70 S6K (phospho Thr421/Ser424) protein at cytoplasm by immunohistochemical analysis in the presence of control peptide (left) or antigen-specific peptide (right). (genetex.com)

Cell3

• Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. (bvsalud.org)
• This makes kinase signaling particularly amenable to comparative studies, and kinase activity a particularly good readout of the physiological state of any cell. (wormbook.org)
• In addition to mutated proteins, NSCLC can over-express a number of non-mutated proteins that can induce both humoral and cytotoxic T cell responses [ 10 ], and also have the potential to serve as tumor rejection antigens [ 11 ]. (biomedcentral.com)