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Updated: Jun 18, 2026
11:13
Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Rictor is a novel target of p70 S6 kinase-1
C Treins1, P H Warne, M A Magnuson
1Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK.
Oncogene
|November 26, 2009
Summary
Researchers found that Rictor, a protein in mTOR complex-2 (mTORC2), is phosphorylated by S6K1. This phosphorylation regulates mTORC2 interactions, influenced by nutrients and growth factors.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Biochemistry
Background:
- The mammalian target of rapamycin (mTOR) complex-2 (mTORC2) is crucial for cell signaling, phosphorylating AGC kinases.
- Rictor is a key component of mTORC2, regulating its activity.
- Understanding mTORC2 regulation is vital for comprehending cellular responses to nutrients and growth factors.
Purpose of the Study:
- To identify novel phosphorylation sites on Rictor.
- To investigate the signaling pathways regulating Rictor phosphorylation.
- To determine the functional consequences of Rictor phosphorylation, particularly at Thr1135.
Main Methods:
- Phosphoproteomic analysis to identify novel phosphorylation sites on Rictor.
- Biochemical assays to confirm Rictor as a direct target of S6K1.
- Site-directed mutagenesis to study the role of Thr1135 phosphorylation.
- Analysis of 14-3-3 protein binding to Rictor and mTORC2.
Main Results:
- Several novel Rictor phosphorylation sites were identified, including the conserved Thr1135.
- Rictor is a direct substrate of ribosomal protein S6 kinase-1 (S6K1).
- Phosphorylation of Rictor at Thr1135 is regulated by amino acids and growth factors via a rapamycin-sensitive pathway.
- Thr1135 phosphorylation mediates 14-3-3 binding to Rictor and mTORC2, impacting complex interactions without altering kinase activity.
Conclusions:
- Rictor phosphorylation by S6K1 represents an unexpected signaling input into mTORC2.
- This regulatory mechanism allows mTORC2 to integrate signals from amino acids and growth factors.
- The dynamic regulation of Rictor phosphorylation and subsequent 14-3-3 binding provides a mechanism for modulating mTORC2 complex interactions.
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