Joseph Avruch
Showed in 1998 that amino acids, not only insulin, are needed for mTOR to activate S6K1 and 4E-BP1. His Massachusetts General Hospital group, with Kazuyoshi Yonezawa's lab in Kobe, then co-discovered raptor in 2002 and found that Rheb binds mTOR directly
Professor of Medicine, Harvard Medical School · Chief, Diabetes Unit, Massachusetts General Hospital (since 1979) · MD, Washington University in St. Louis
Profile, MGH Research Institute (Boston, Massachusetts, USA) ↗
Joseph Avruch has led the Diabetes Unit at Massachusetts General Hospital since 1979, building a career tracing how insulin and growth-factor signalling control protein synthesis and cell growth — work that converged on mTOR as insulin's downstream growth-control checkpoint.
Together with Kazuyoshi Yonezawa's lab in Kobe, his lab identified raptor as mTOR's nutrient-sensitive binding partner in 2002 (in parallel with the Sabatini lab), and in 2005 showed that the small GTPase Rheb binds directly to mTOR's kinase domain and activates it. Together with the 2003 reports from several groups that Rheb is the target of the TSC1/TSC2 complex, this identified Rheb as a direct activator of mTORC1.
The timeline below follows Avruch's contributions gathered in this Atlas.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 1992 | M | Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase PRI1992 Co-author: rapamycin inactivates the 70-kDa S6 kinase, an early readout of TOR signalling (cells). |
| 1998 | M | Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism HAR1998 Shows amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism, among the earliest evidence linking nutrients directly to mTOR substrates. |
| 2002 | M | Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action HARA2002 Independently identifies raptor as a binding partner of mTOR that mediates its action, alongside the Sabatini lab's 2002 raptor paper. |
| 2003 | M | The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif NOJ2003 Raptor binds mTOR substrates via their TOS motifs, acting as the substrate-presenting scaffold of mTORC1. |
| 2005 | M | Rheb binds and regulates the mTOR kinase LON2005 Shows Rheb binds directly to mTOR and regulates its kinase activity, establishing Rheb as mTOR's direct GTPase activator. |
| 2007 | M | The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1 OSH2007 PRAS40 is a physiological raptor-bound substrate and inhibitor of mTORC1. |
Co-authors in the Atlas 8
People with a profile here who share at least one study with Joseph Avruch.
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- Kazuyoshi Yonezawa 5 shared studies Led the Kobe University group that co-discovered raptor in 2002, in parallel with the Sabatini lab. His team then showed that raptor binds mTOR's substrates through their TOS motif and that PRAS40 is itself an mTORC1 substrate
- Kenta Hara 4 shared studies Showed in 1998 that amino acids are needed for mTOR to activate S6K1 and 4E-BP1, and as first author co-discovered raptor in 2002
- Noriko Oshiro-Rapley 3 shared studies In one of several 2007 studies, identified PRAS40 as a raptor-bound mTORC1 substrate that gates access to mTORC1's other substrates
- Chiharu Tokunaga 2 shared studies Member of Kazuyoshi Yonezawa's Kobe team that co-discovered raptor, and first author of a 2004 review on how mTOR combines amino acid and energy signals
- Sujuti Hidayat 2 shared studies Member of Kazuyoshi Yonezawa's Kobe team that co-discovered raptor and worked out how mTOR senses amino acids, and first author of a study showing that a leucine derivative can block amino acid-mTOR signalling
- Xiaomeng Long 2 shared studies Discovered that Rheb binds directly to the mTOR kinase domain and switches it on
- Barbara E. Bierer Haematologist-oncologist and research-ethics leader whose early lab work helped show how rapamycin acts on immune cells
- Hiroki Nojima First author of the 2003 Kobe study showing that raptor grabs mTOR's targets through a short TOS motif, the docking step that lets mTORC1 reach its substrates
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