p70S6K Antibody – Rabbit Polyclonal

Function: Acts to integrate nutrient and growth factor signals in regulation of protein synthesis, cell proliferation, cell growth, cell cycle progression and cell survival. Downstream effector of the mTOR signaling pathway. Phosphorylates specifically ribosomal protein S6 in response to insulin or several classes of mitogens. During translation initiation, the inactive form interacts with the eIF-3 complex under conditions of nutrient depletion. Mitogenic stimulation leads to phosphorylation and dissociation from the eIF-3 complex and the free activated form can phosphorylate other translational targets including EIF4B. Promotes protein synthesis by phosphorylating PDCD4 at 'Ser-67' and targeting it for degradation. Phosphorylates RICTOR leading to regulation of mammalian target of rapamycin complex 2 (mTORC2) signaling. Phosphorylates IRS1 at multiple serine residues coupled with insulin resistance. Required for TNF-alpha induced IRS-1 degradation. Phosphorylates EEF2K in response to IGF1 and inhibits EEF2K activity. Phosphorylates BAD in response to IGF1 leading to BAD inactivation and inhibition of BAD-induced apoptosis. Phosphorylates mitochondrial RMP leading to dissociation of a RMP:PPP1CC complex. The free mitochondrial PPP1CC can dephosphorylate RPS6KB1 at Thr-412 which is proposed to be a negative feed back mechanism for the RPS6KB1 antiapoptotic function. Phosphorylates POLDIP3

Catalytic activity: ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation: Activated by serine/threonine phosphorylation and protein kinase C, inactivated by type 2A phosphatase. Activation requires multiple phosphorylatiopn events. Activation appears to be first mediated by multiple phosphorylation in the autoinhibitory domain, which facilitates phosphorylation at Thr-412 by disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252. The active conformation of the kinase is believed to be stablilized 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; sensitive for rapamycin, which inhibits phosphorylation at Thr-412. Activated by PDPK1

Subunit structure: Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with POLDIP3 and TRAF4

Subcellular location: Cytoplasm

By similarity. Cell junction › synapse › synaptosome

By similarity. Mitochondrion outer membrane

Domain: The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop

By similarity.The TOS (TOR signaling) motif is essential for activation by mTORC1

Post-translational modification: Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism

Sequence similarities: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.Contains 1 AGC-kinase C-terminal domain.Contains 1 protein kinase domain.