RPS6KB1 phosphorylates the Ribosomal Protein-S6. Activation of RPS6KB1 requires a complex, ordered series of conformational changes and phosphorylation reactions. While the role of sequential, multi-site phosphorylation has been extensively detailed, characterization of the priming step required to initiate this cascade has remained elusive. Probably this priming process is dependent on calcium. Calcium-dependent regulation of RPS6KB1 does not specifically target Thr-229 and Thr-389, the key regulatory phosphorylation sites; rather, calcium chelation results in a global inhibition of RPS6KB1 phosphorylation. The initial calcium-dependent process is required to release an inhibitory interaction between the C- and N-termini of RPS6KB1, thus allowing phosphorylation of key domains. The priming event involves formation of a calcium-dependent protein complex that releases the interaction between the N- and C-termini. RPS6KB1 is then accessible for activation by the kinases that target the known regulatory phosphorylation sites . Satoru Eguchi et al. (1999) J Biol Chem, Vol. 274: 36843-36851 Papst PJ, et al. (1998) J Biol Chem. 273(24):15077-84. Ulrike Krause et al. (2002) Eur. J. Biochem. 269: 3751-3759 c Le, X.F, et al. (2003) Oncogene 22: 484
Host
Rabbit
Immunogen
Peptide sequence around aa.422~426 (P-V-S-P-V) derived from Human p70S6k.
Raised In
Rabbit
Reactivity
Human, Mouse, Rat
Regulatory
RUO
Relevance
RPS6KB1 phosphorylates the Ribosomal Protein-S6. Activation of RPS6KB1 requires a complex, ordered series of conformational changes and phosphorylation reactions. While the role of sequential, multi-site phosphorylation has been extensively detailed, characterization of the priming step required to initiate this cascade has remained elusive. Probably this priming process is dependent on calcium. Calcium-dependent regulation of RPS6KB1 does not specifically target Thr-229 and Thr-389, the key regulatory phosphorylation sites; rather, calcium chelation results in a global inhibition of RPS6KB1 phosphorylation. The initial calcium-dependent process is required to release an inhibitory interaction between the C- and N-termini of RPS6KB1, thus allowing phosphorylation of key domains. The priming event involves formation of a calcium-dependent protein complex that releases the interaction between the N- and C-termini. RPS6KB1 is then accessible for activation by the kinases that target the known regulatory phosphorylation sites .
Satoru Eguchi et al. (1999) J Biol Chem, Vol. 274: 36843-36851 Papst PJ, et al. (1998) J Biol Chem. 273(24):15077-84. Ulrike Krause et al. (2002) Eur. J. Biochem. 269: 3751-3759 c Le, X.F, et al. (2003) Oncogene 22: 484
Species
Homo Sapiens (Human)
Specificity
The antibody detects endogenous level of total p70 S6 Kinase protein.
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.
Protein kinase superfamily, AGC Ser/Thr protein kinase family, S6 kinase subfamily
Tissue Specificity
Widely expressed.
Buffer
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Form
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Format
liquid
Purification
Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
Purity
Antibodies were produced by immunizing rabbits with synthetic peptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitope-specific peptide.
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.