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Ribosomal protein S6 kinase

Serine/threonine kinase that may play a role in mediating the growth-factor and stress induced activation of transcription.

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Ribosomal protein S6 kinase 2 alpha

Also known as Ribosomal protein S6 kinase 2 alpha (MAP kinase-activated protein kinase 1) (MAPK-activated protein kinase 1) (MAPKAP kinase 1) (MAPKAPK-1) (Ribosomal protein S6 kinase II alpha) (S6KII-alpha) (p90-RSK).
p90RSK: an AGC kinase of the RSK family. Phosphorylated and activated by Erk1 and -2 in response to many growth factors, polypeptide hormones and neurotransmitters. Several phosphorylation sites are important for its activation. Possesses two kinase domains connected by a regulator linker region. Phosphorylates a wide range of substrates including ribosomal protein S6. Prominently expressed in brain structures essential for cognitive function and learning.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; RSK subfamily; Translation

Cellular Component: cytoplasm; nucleus

Molecular Function: protein serine/threonine kinase activity

Ribosomal protein S6 kinase alpha-1

Also known as Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6.
p90RSK: an AGC kinase of the RSK family. Phosphorylated and activated by Erk1 and -2 in response to many growth factors, polypeptide hormones and neurotransmitters. Several phosphorylation sites are important for its activation. Possesses two kinase domains connected by a regulator linker region. Phosphorylates a wide range of substrates including ribosomal protein S6. Prominently expressed in brain structures essential for cognitive function and learning.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; RSK subfamily; Translation

Cellular Component: cytoplasm; nucleus; spindle

Molecular Function: caspase inhibitor activity; kinase activity; protein serine/threonine kinase activity; protein serine/threonine/tyrosine kinase activity; transcription factor binding

Biological Process: negative regulation of apoptosis; negative regulation of caspase activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; protein amino acid phosphorylation

Ribosomal protein S6 kinase alpha-2

Also known as Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Protein-tyrosine kina.
RSK3: an AGC kinase of the RSK family. Phosphorylated and activated by Erk1 and -2 in response to many growth factors, polypeptide hormones and neurotransmitters. Several phosphorylation sites are important for its activation. Possesses two kinase domains connected by a regulator linker region. Phosphorylates a wide range of substrates including ribosomal protein S6.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; RSK subfamily; Translation; Tumor suppressor

Cellular Component: cytoplasm; nuclear membrane; nucleoplasm; nucleus; spindle

Molecular Function: protein binding; protein kinase activity; protein serine/threonine kinase activity; protein serine/threonine/tyrosine kinase activity; ribosomal protein S6 kinase activity

Biological Process: brain renin-angiotensin system; heart contraction; heart development; negative regulation of cell cycle; negative regulation of cell proliferation; negative regulation of meiosis; oocyte maturation; peptidyl-serine phosphorylation; positive regulation of apoptosis; protein amino acid phosphorylation

Ribosomal protein S6 kinase alpha-3

Also known as Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP.
RSK2: an AGC kinase of the RSK family. Phosphorylated and activated by Erk1 and -2 in response to many growth factors, polypeptide hormones and neurotransmitters. Several phosphorylation sites are important for its activation. Possesses two kinase domains connected by a regulator linker region. Phosphorylates a wide range of substrates including ribosomal protein S6. Prominently expressed in brain structures essential for cognitive function and learning.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; RSK subfamily

Chromosomal Location of Human Ortholog: Xp22.2-p22.1

Cellular Component: cytoplasm; cytosol; nucleoplasm; nucleus

Molecular Function: caspase inhibitor activity; kinase activity; protein binding; protein kinase activity; protein serine/threonine kinase activity

Biological Process: central nervous system development; negative regulation of apoptosis; negative regulation of caspase activity; positive regulation of cell differentiation; positive regulation of cell growth; positive regulation of transcription from RNA polymerase II promoter; regulation of transcription in response to stress; regulation of translation in response to stress; response to lipopolysaccharide; signal transduction; skeletal development; toll-like receptor signaling pathway

Disease: Coffin-lowry Syndrome; Mental Retardation, X-linked 19

Ribosomal protein S6 kinase alpha-4

Also known as Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB).
MSK2: an AGC kinase of the RSK family. Has two kinase domains connected by a regulatory linker region. Phosphorylates H3 and HMG-14 in response to growth factors and cellular stress.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; MSK subfamily; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family

Chromosomal Location of Human Ortholog: 11q11-q13

Cellular Component: cytoplasm; nucleoplasm; nucleus

Molecular Function: ATP binding; histone serine kinase activity (H3-S10 specific); mitogen-activated protein kinase p38 binding; protein binding; protein serine/threonine kinase activity

Biological Process: activation of CREB transcription factor; activation of NF-kappaB transcription factor; histone phosphorylation; negative regulation of cytokine production; positive regulation of histone acetylation; positive regulation of histone phosphorylation; positive regulation of transcription from RNA polymerase II promoter; protein amino acid phosphorylation; regulation of transcription, DNA-dependent

Ribosomal protein S6 kinase alpha-5

Also known as Ribosomal protein S6 kinase alpha-5 (S6K-alpha-5).
Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury ().

Ribosomal protein S6 kinase alpha-6

Also known as Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6).
RSK4: an AGC kinase of the RSK family. Phosphorylates a wide range of substrates including ribosomal protein S6. Implicated in the activation of the mitogen- activated kinase cascade. May play a role in normal neuronal development.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSK family; RSK subfamily

Cellular Component: cytoplasm; mitochondrion; nucleolus; nucleoplasm; nucleus

Molecular Function: protein serine/threonine kinase activity

Biological Process: DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; negative regulation of embryonic development

Ribosomal protein S6 kinase beta

Serine/threonine-protein kinase which regulates mRNA translation (PubMed:17266680). Negatively regulates lifespan and resistance to starvation, oxidative stress, protein aggregation and P.aeruginosa-mediated infection (PubMed:17266680, PubMed:23879233, PubMed:24332851). May regulate these processes by preventing the activation of transcription factor hif-1 (PubMed:23879233). Required, probably downstream of let-363/TOR, for the establishment of the proper number of germline progenitors by promoting cell cycle progression and preventing differentiation during larval development. Regulates germ cell size (PubMed:22278922). In addition required for sperm production and embryo viability (PubMed:17266680, PubMed:22278922). Involved in axon regeneration of PLM and ALM neurons by inhibiting growth cone formation early after axotomy and later by inhibiting axon extension. Functions in axon regeneration and lifespan probably by preventing aak-2/AMPK activation (PubMed:24332851, PubMed:24431434). Negatively regulates autophagy (PubMed:22560223).

Ribosomal protein S6 kinase beta-1

Also known as Ribosomal protein S6 kinase beta-1 (S6K-beta-1) (S6K1) (70 kDa ribosomal protein S6 kinase 1) (P70S6K1) (p70-S6K 1).
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 RMP leading to dissociation of a RMP: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 ().

Ribosomal protein S6 kinase beta-2

Also known as Ribosomal protein S6 kinase beta-2 (S6K-beta-2) (S6K2) (70 kDa ribosomal protein S6 kinase 2) (p70 ribosomal S6 kinase beta) (p70 S6 kinase beta) (p70 S6K-beta) (p70 S6KB).
P70S6KB: an AGC kinase of the RSK family that is required for cell growth and G1 cell cycle progression. Is phosphorylated and activated by mTOR in mitogenic pathways downstream of phosphoinositide 3 kinase (PI3K). Phosphorylates the S6 protein of the 40S ribosomal subunit and is involved in translational control of 5' oligopyrimidine tract mRNAs. Activity is controlled by multiple phosphorylation events located within the catalytic, linker and pseudosubstrate domains. Mouse knockout shows symptoms of insulin resistance, and increased insulin senstivity, resulting in protection against diet-induced obesity. Protein expression and activation upregulated in colon adenocarcinoma cell lines. Increased expression in breast cancer correlated with poor survival. Selectively amplified and overexpressed within the 17q23 breast cancer amplicon. Two isoforms produced by alternative initiation have been reported.

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

Cellular Component: cytoplasm; nucleus

Molecular Function: ATP binding; peptide binding; protein kinase activity; ribosomal protein S6 kinase activity

Biological Process: positive regulation of translational initiation; protein amino acid phosphorylation; protein kinase B signaling cascade

Ribosomal protein S6 kinase delta-1

Also known as Ribosomal protein S6 kinase delta-1 (S6K-delta-1) (52 kDa ribosomal protein S6 kinase).
RSKL1: an AGC kinase of the RSKL family.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSKL family

Cellular Component: cytoplasm; early endosome; intracellular membrane-bound organelle

Molecular Function: protein serine/threonine kinase activity

Biological Process: signal transduction

Ribosomal protein S6 kinase-like 1

RSKL2: an AGC kinase of the RSKL family.

Protein type: AGC group; EC 2.7.11.1; Kinase, protein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor); RSKL family

Cellular Component: cytoplasm; intracellular membrane-bound organelle

Molecular Function: protein serine/threonine kinase activity

Biological Process: signal transduction

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