RPS6KB1 - Ribosomal protein S6 kinase beta-1 - human protein (Function)
 
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RPS6KB1 »  Ribosomal protein S6 kinase beta-1   [ EC 2.7.11.1 ]  (S6K1)
 
Protein also known as:  70 kDa ribosomal protein S6 kinase 1 (P70S6K1).
Gene name:  RPS6KB1
Entry whose protein(s) existence is based on evidence at protein level
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1 176 4
GENE REF ISO

Function

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Overview 
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 preinitiation 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.  
15
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
Peptide bindingdefinition[GO:0042277] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
5
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
3
  • IDAUniProtKB
Ribosomal protein S6 kinase activitydefinition[GO:0004711] silver  
  • IEAOrtholog Compara
GO biological process 
Agingdefinition[GO:0007568] silver  
  • IEAOrtholog Compara
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Cell migrationdefinition[GO:0016477] silver  
  • IEAOrtholog Compara
Cellular response to growth factor stimulusdefinition[GO:0071363]  
1
  • IDAUniProtKB
G1/S transition of mitotic cell cycledefinition[GO:0000082]  
1
  • IMPUniProtKB
Germ cell developmentdefinition[GO:0007281] silver  
  • IEAOrtholog Compara
Long-term memorydefinition[GO:0007616] silver  
  • IEAOrtholog Compara
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Negative regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001237] silver  
  • IEAOrtholog Compara
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
1
  • IMPUniProtKB
Phosphatidylinositol-mediated signalingdefinition[GO:0048015]  
1
  • TASUniProtKB
Positive regulation of mitotic cell cycledefinition[GO:0045931]  
1
  • IMPUniProtKB
Positive regulation of skeletal muscle tissue growthdefinition[GO:0048633] silver  
  • IEAOrtholog Compara
Positive regulation of smooth muscle cell migrationdefinition[GO:0014911] silver  
  • IEAOrtholog Compara
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
  • IEAOrtholog Compara
Positive regulation of translationdefinition[GO:0045727]  
1
  • IMPUniProtKB
Positive regulation of translational initiationdefinition[GO:0045948]  
1
  • IMPUniProtKB
Protein kinase B signalingdefinition[GO:0043491] silver  
  • IEAOrtholog Compara
Isoforms  Alpha I and Alpha II   Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAGOC
Regulation of glucose importdefinition[GO:0046324] silver  
  • IEAOrtholog Compara
Response to drugdefinition[GO:0042493] silver  
  • IEAOrtholog Compara
Response to electrical stimulus involved in regulation of muscle adaptationdefinition[GO:0014878] silver  
  • IEAOrtholog Compara
Response to ethanoldefinition[GO:0045471] silver  
  • IEAOrtholog Compara
Response to glucagondefinition[GO:0033762] silver  
  • IEAOrtholog Compara
Response to glucocorticoiddefinition[GO:0051384] silver  
  • IEAOrtholog Compara
Response to glucosedefinition[GO:0009749] silver  
  • IEAOrtholog Compara
Response to heatdefinition[GO:0009408] silver  
  • IEAOrtholog Compara
Response to leucinedefinition[GO:0043201] silver  
  • IEAOrtholog Compara
Response to lipopolysaccharidedefinition[GO:0032496] silver  
  • IEAOrtholog Compara
Response to mechanical stimulusdefinition[GO:0009612] silver  
  • IEAOrtholog Compara
Response to nutrientdefinition[GO:0007584] silver  
  • IEAOrtholog Compara
Response to testosteronedefinition[GO:0033574] silver  
  • IEAOrtholog Compara
Response to toxic substancedefinition[GO:0009636] silver  
  • IEAOrtholog Compara
Response to tumor necrosis factordefinition[GO:0034612] silver  
  • IEAOrtholog Compara
Response to woundingdefinition[GO:0009611] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Skeletal muscle atrophydefinition[GO:0014732] silver  
  • IEAOrtholog Compara
Skeletal muscle contractiondefinition[GO:0003009] silver  
  • IEAOrtholog Compara
TOR signalingdefinition[GO:0031929]  
1
  • IDAUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1.  
3
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+6198  
ErbB signaling pathway  hsa04012+6198  
Fc gamma R-mediated phagocytosis  hsa04666+6198  
Insulin signaling pathway  hsa04910+6198  
mTOR signaling pathway  hsa04150+6198  
TGF-beta signaling pathway  hsa04350+6198  
According to Reactome, this protein belongs to the following pathway:
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Translation regulation  definition   [KW-0810]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: P70-S6_Kinase_1
GenomeRNAi: 6198
PRO: PR:P23443
Chemistry
GuidetoPHARMACOLOGY: 1525