Paul Tempst
Developed mass-spectrometry methods for identifying proteins from tiny samples, and led the Memorial Sloan Kettering proteomics laboratory that identified the unknown partners of mTOR in the raptor, mLST8 and rictor purifications
Molecular Biology Program, Memorial Sloan Kettering Cancer Center · mass-spectrometry protein identification
Tempst Lab, Sloan Kettering Institute (New York, New York, USA) ↗ ORCID0000-0002-6680-3987 ↗
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
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 1994 | M | RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs SAB1994 Discovery of the protein RAFT1 (today's mTOR) as the direct target of the FKBP12-rapamycin complex; one of three 1994 reports (with Brown et al. and Chiu et al.) that identified mammalian TOR, three years after TOR was found in yeast. |
| 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. |
Co-authors in the Atlas 8
People with a profile here who share at least one study with Paul Tempst.
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- Hediye Erdjument-Bromage 5 shared studies Ran the mass-spectrometry analyses in Paul Tempst's lab at Memorial Sloan Kettering that identified the unknown proteins in the raptor, mLST8 and rictor purifications, and contributed the same approach to work on how ERK inactivates TSC2
- David M. Sabatini 4 shared studies Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Do-Hyung Kim 3 shared studies Co-discovered raptor, the defining partner of mTOR in mTORC1, and then mLST8 (GbetaL) as a Sabatini-lab postdoc. His Minnesota lab identified PRAS40 as an insulin-regulated link to mTORC1 and studies how mTORC1 controls autophagy
- Dos D. Sarbassov 3 shared studies Discovered rictor as a Sabatini-lab postdoc, in parallel with Michael Hall's lab, defining mTOR Complex 2, and showed that this complex is the long-sought kinase that phosphorylates Akt on serine 473. He also found that prolonged rapamycin treatment can block mTORC2 assembly
- Robert R. Latek 3 shared studies Bioinformatics scientist at the Whitehead Institute who worked on the Sabatini-lab papers that described raptor, mLST8 (GbetaL) and rictor (raptor and rictor were reported in parallel by other labs), the core partners of mTOR in its two complexes
- Siraj M. Ali 3 shared studies Worked in the Sabatini lab on the papers that discovered raptor, mLST8 and rictor, and on the finding that the rictor-mTOR complex phosphorylates Akt. He later moved into cancer genomics and clinical diagnostics
- David A. Guertin Built the mouse genetics that defined mTORC2's biological roles
- Pier Paolo Pandolfi Showed that ERK directly phosphorylates and inactivates TSC2, wiring Ras/MAPK signalling into mTORC1 control, and that blocking mTORC1 in patients' tumours triggers a feedback rise in MAPK signalling
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