Rabbit Anti-RPS6KB1 Polyclonal Antibody#abs136433

abs136433-100ug

1-2 Weeks

301.0

abs136433-50ug

1-2 Weeks

201.0

catalog

Description

p70 S6 kinase is a protein kinase that plays a crucial role in cell growth and progression through the G1 phase of the cell cycle. It achieves this by phosphorylating the S6 protein that is part of the ribosomal subunit. There are two isoforms of p70 S6 kinase, with the p85 form differing only slightly due to an additional 23 amino acids at its amino terminus. These isoforms are part of a signaling pathway that originates from PI-3K and the FRAP/mTOR target, which is distinct from the Ras/MAP kinase cascade.
Several phosphorylation events occur within the catalytic, linker, and pseudosubstrate domains to regulate the activity of p70 S6 kinase. However, phosphorylation at Thr389 in the linker domain is critical for kinase function. The action of PDK1 on Thr229 within the catalytic domain requires prior phosphorylation of Thr389. Cells stimulated by insulin, EGF, or FGF as well as serum and some G-protein-coupled receptor ligands result in the phosphorylation of p70 S6 kinase, and this is blocked by wortmannin, LY294002 (PI-3K inhibitor), and rapamycin (FRAP/mTOR inhibitor).
Phosphorylation at Ser411, Thr421, and Ser424, all located within the pseudosubstrate region, activate p70 S6 kinase by relieving pseudosubstrate suppression. Additionally, Ser371, which is an in vitro substrate for mTOR and is sensitive to LY294002 and rapamycin phosphorylation, correlates with the activity of a partially rapamycin-resistant mutant of p70 S6 kinase. Overall, these phosphorylation events are essential for the proper activation and function of p70 S6 kinase in the cell.

Concentration

1mg/ml

Target

Background

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.