RPS6KB1

This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17.

Ribosomal Protein S6 Kinase B1

Ribosomal Protein S6 Kinase B1; Serine/Threonine-Protein Kinase 14A; Ribosomal Protein S6 Kinase I; EC 2.7.11.1; S6K-Beta-1; P70 S6KA; STK14A; S6K1; Ribosomal Protein S6 Kinase, 70kDa, Polypeptide 1; Ribosomal Protein S6 Kinase, 70kD, Polypeptide 1; 70 KDa Ribosomal Protein S6 Kinase 1; Ribosomal Protein S6 Kinase Beta-1; Serine/Threonine Kinase 14 Alpha;

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).

AgingIEA:Ensembl
Apoptotic processIEA:UniProtKB-KW
Behavioral fear responseIEA:Ensembl
Cell migrationIEA:Ensembl
Cellular response to dexamethasone stimulusIEA:Ensembl
Cellular response to growth factor stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to insulin stimulusManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to interferon-gammaIEA:Ensembl
G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIMP:UniProtKB
Germ cell developmentIEA:Ensembl
Long-chain fatty acid import into cellISS:UniProtKB
Long-term memoryIEA:Ensembl
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of extrinsic apoptotic signaling pathwayIEA:Ensembl
Negative regulation of insulin receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Phosphatidylinositol-mediated signalingManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of mitotic cell cycleManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of skeletal muscle tissue growthIEA:Ensembl
Positive regulation of smooth muscle cell migrationIEA:Ensembl
Positive regulation of smooth muscle cell proliferationIEA:Ensembl
Positive regulation of translationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of translational initiationManual Assertion Based On ExperimentIMP:UniProtKB
Protein kinase B signalingIEA:Ensembl
Regulation of glucose importIEA:Ensembl
Response to electrical stimulus involved in regulation of muscle adaptationIEA:Ensembl
Response to ethanolIEA:Ensembl
Response to glucagonIEA:Ensembl
Response to glucoseIEA:Ensembl
Response to heatIEA:Ensembl
Response to leucineIEA:Ensembl
Response to lipopolysaccharideIEA:Ensembl
Response to mechanical stimulusIEA:Ensembl
Response to nutrientIEA:Ensembl
Response to nutrient levelsManual Assertion Based On ExperimentIDA:UniProtKB
Response to testosteroneIEA:Ensembl
Response to toxic substanceIEA:Ensembl
Response to tumor necrosis factorIEA:Ensembl
Response to woundingIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Skeletal muscle atrophyIEA:Ensembl
Skeletal muscle contractionIEA:Ensembl
TOR signalingManual Assertion Based On ExperimentIDA:UniProtKB

Cell junction, synapse, synaptosome
Mitochondrion outer membrane
Mitochondrion
Colocalizes with URI1 at mitochondrion.
Isoform Alpha I
Nucleus
Cytoplasm
Isoform Alpha II
Cytoplasm

Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism (By similarity).
Activated by phosphorylation at Thr-252 by PDPK1. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion.