Paul Tempst
Built the mass-spectrometry protein-identification methods that made the mTOR complex purifications readable
Molecular Biology Program, Memorial Sloan Kettering Cancer Center · pioneer of mass-spectrometry protein identification
Tempst Lab, Sloan Kettering Institute ↗
Paul Tempst built his career developing the technology and methods used to identify proteins and their modifications by mass spectrometry, work that made his laboratory's proteomics core at Memorial Sloan Kettering Cancer Center one of the reference facilities for the field. His techniques for polypeptide isolation and mass-spectrometric sequencing let researchers elsewhere identify unknown proteins from vanishingly small biochemical samples.
That capability was decisive for David Sabatini's lab when it purified mTOR-associated proteins and needed to know exactly what it had pulled down: Tempst's core identified raptor and rictor, the subunits that founded mTORC1 and mTORC2 respectively. The discoveries below, gathered in this Atlas, rest on that proteomics work.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2002 | M | mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery KIM2002 Mass-spectrometry identification of raptor, the defining subunit of mTORC1. |
| 2003 | M | GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR KIM2003 Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex. |
| 2004 | M | Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton SAR2004 Mass-spectrometry identification of rictor, the defining subunit of mTORC2. |
| 2005 | M | Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis MA2005 The MAPK input to mTORC1. In mammalian cells, ERK phosphorylates TSC2 and inactivates the TSC complex, so growth signalling through Ras/ERK converges on the same brake that Akt releases. This is the third major upstream arm alongside PI3K/Akt and AMPK. Its practical significance is that it offers a route to mTORC1 activation that PI3K inhibitors do not close - though that inference is mechanistic; no human data here. |