O. Jameel Shah
Cell biologist in Tony Hunter's lab at the Salk Institute who showed that runaway Rheb-mTOR-S6K signalling destroys the insulin receptor's helper proteins IRS1 and IRS2, one half of the discovery of the S6K-IRS feedback loop
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies (Tony Hunter lab, at the time of the study)
When insulin binds its receptor, the signal passes through helper proteins called IRS1 and IRS2 before it reaches Akt and, further down, mTORC1 and its target S6K. O. Jameel Shah's 2004 paper in Current Biology (SHA2004), from Tony Hunter's lab at the Salk Institute, showed what happens when the end of that chain is stuck on. In cultured mammalian cells lacking the TSC brake, constant activity of Rheb, mTOR and S6K led to the loss of IRS1 and IRS2. The cells became resistant to insulin and their survival signalling through Akt weakened.
The paper appeared two months after a companion study by Harrington and colleagues, and together they set out the S6K-to-IRS negative feedback loop. In this loop, an overactive mTORC1 pathway turns down the very insulin signal that feeds it. The work was done in cultured cells.
PubMed lists Shah at the Salk Institute at the time of the study. Because PubMed also indexes an unrelated surgeon with the same initials, a full publication record could not be built safely, and no current position could be confirmed.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2004 | M | Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies SHA2004 First author: showed in cultured cells that constitutive Rheb/mTOR/S6K signalling depletes IRS1 and IRS2, causing insulin resistance and weaker survival signalling. |
Co-authors in the Atlas 1
People with a profile here who share at least one study with O. Jameel Shah.
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- Tony Hunter Cell biologist who showed that tyrosine phosphorylation is a master on/off switch for proteins, work that informed cancer drugs such as Gleevec; his lab also studied the TSC/Rheb/mTOR/S6K feedback to insulin signalling.
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