Pathway link IRS1-PI3K
IRS-1 / IRS-2 PI3K
IRS-1 / IRS-2 activates PI3K.
IRS proteins carry the signal from the insulin receptor to PI3K; without them, the receptor is still there but the wire connecting it is cut.
The conditions it holds under
Cell studies (TSC1/TSC2-null mouse cells and human cells) plus a review. An adaptor relationship shown in cultured cells; differences between IRS-1 and IRS-2 by tissue are not resolved by these sources.
- Time it takes
- seconds
- Step
- direct (one molecule acts on the other)
- Measured in
- mammalian cells
- Where in the cell
- plasma membrane
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2004 | M | The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteinsHAR2004 One of two 2004 papers that placed mTORC1's main negative feedback loop downstream of TSC-Rheb-S6K1 (rapamycin-sensitive IRS-1 degradation had been reported earlier, Haruta 2000). When mTORC1/S6K1 activity is left switched on, S6K1 phosphorylates IRS-1 and represses its expression, so the insulin receptor can no longer signal to PI3K. This is the textbook explanation for why blocking mTORC1 paradoxically raises Akt activity, and it contributes to insulin resistance when mTORC1 is chronically overactive (for example with TSC loss or nutrient excess). The insulin resistance seen with chronic rapamycin is instead attributed mainly to mTORC2 disruption (LAM2012). |
| 2002 | R | The phosphoinositide 3-kinase pathwayCAN2002 Review establishing PI3K as a central signaling hub controlling cell survival, metabolism, and growth downstream of growth-factor receptors and upstream of Akt and mTOR. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
← The whole pathway · This link as JSON
Was this page useful?
Thank you. Your answer was counted anonymously.
Spotted something wrong or out of date about this link?
Thank you. That helps us know which pages have been read by someone who knows the work.
Thank you. We will check it and correct the page.