| p70S6K (RPS6KB1) | |
|---|---|
| Gene | [RPS6KB1](/genes/rps6kb1) |
| UniProt | Q9UQK2 |
| PDB | 3WE, 4XS0 |
| Mol. Weight | ~70 kDa |
| Localization | Cytoplasm, Nucleus, Synaptic vesicles |
| Family | AGC kinase family (PKC/PKB/P70S6K) |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Diabetes](/diseases/diabetes), [Cancer](/diseases/cancer) |
p70S6K (ribosomal protein S6 kinase beta-1), also known as RPS6KB1 or S6K1, is a serine/threonine protein kinase that plays central roles in regulating protein synthesis, cell growth, and metabolic processes. It is a key downstream effector of the mTOR (mechanistic target of rapamycin) signaling pathway and has been implicated in various neurodegenerative diseases including Alzheimer's disease and Parkinson's disease[1].
p70S6K (RPS6KB1) is a member of the AGC (PKA/PKB/PKC) family of serine/threonine kinases. It exists as two isoforms (p70S6Kα1 and p70S6Kα2) generated by alternative splicing. p70S6K is activated by growth factors, nutrients, and cellular energy status through the mTORC1 pathway. Once activated, it phosphorylates numerous substrates to regulate translation, transcription, cell cycle progression, and metabolic processes[2].
p70S6K is a serine/threonine kinase with a complex domain architecture:
p70S6K has two isoforms:
p70S6K activation requires:
p70S6K is a key regulator of translation:
p70S6K is the primary effector of mTORC1:
In neurons, p70S6K:
p70S6K influences cellular metabolism:
p70S6K is centrally implicated in AD:
In PD, p70S6K:
p70S6K is a therapeutic target:
Burnett PE, Blackenberg S, Choi S, et al. Cloning, expression, and crystal structure of human p70 S6 kinase. 1998. ↩︎
Fingar DC, Blenis J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. 2004. ↩︎
Saitoh M, Pullen N, Brennan P, et al. Regulation of an activated S6 kinase 1 identifies a novel protein kinase cascade. 2002. ↩︎
Ma L, Chen Z, Erdjument-Bromage H, et al. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. 2005. ↩︎
Cai J, Wei W, Li C, et al. p70S6 kinase in the regulation of tau phosphorylation. 2010. ↩︎