Practice Arena

1. A hormone the body releases when food is plentiful
2. A protein kinase — an enzyme that attaches phosphate groups to other proteins
3. A transcription factor that binds DNA at growth genes
4. A structural protein that holds the lysosome together

Answer: B. mTOR is an enzyme. It changes what other proteins do by phosphorylating them, and everything downstream in this course follows from that one activity.

1. RICTOR
2. SIN1
3. RAPTOR
4. mLST8

Answer: C. RAPTOR is the mTORC1-defining partner and RICTOR and SIN1 belong to mTORC2. mLST8 is the distractor worth remembering, because it sits in both complexes.

1. Rheb-GDP
2. Rheb-GTP
3. Both forms equally
4. Neither — Rheb acts only on mTORC2

Answer: B. Rheb is a switch protein whose two nucleotide states behave differently, and it is the GTP-bound state that activates the kinase. Everything the TSC complex does is about how much Rheb-GTP there is.

1. It binds Rheb and physically blocks its interaction with mTORC1
2. It accelerates Rheb's hydrolysis of its own bound GTP, pushing Rheb toward the GDP state
3. It loads Rheb with fresh GTP
4. It degrades Rheb protein

Answer: B. A GTPase-activating protein speeds up a reaction the GTPase already performs. That is why the TSC complex sets a rate rather than flipping a switch, and why the amount of Rheb-GTP is a balance.

1. Rheb
2. The Ragulator complex
3. RAPTOR
4. TFEB

Answer: B. The Rags are not membrane-anchored on their own. Ragulator tethers them to the lysosome and acts on their nucleotide state, which is what makes the surface a platform rather than a passive membrane.

1. Arginine
2. Leucine
3. Glutamine
4. Methionine

Answer: B. Sestrin2 is the leucine-binding protein of this set; CASTOR1 handles arginine and SAMTOR reads S-adenosylmethionine, the metabolite downstream of methionine.

1. That mTOR activity shifts the balance between building programs and recycling programs in the systems where this has been measured
2. That mTOR is the only route to growth, or that removing it stops growth in every cell
3. That several unrelated kinds of information reach the same kinase, which is what makes it worth calling an integrator

Answer: B. Almost everything in this lesson was worked out in cultured cells and in laboratory animals, and the summary sentence compresses a network with many parallel inputs and outputs into one verb. The compression is useful for learning and it is not a finding; when you meet a claim about mTOR and human health later in the Atlas, the evidence tier attached to it is doing real work.

1. That the two complexes differ in composition and in substrates, and that the difference is visible both chemically and genetically
2. That rapamycin blocks some mTORC1 outputs much more completely than others
3. That any compound is selective as a property independent of dose, duration and cell type

Answer: C. Every study cited in this lesson is M or A: biochemistry, cell work and mouse genetics. That is the honest state of complex-level evidence. Selectivity in particular is a claim about an experiment, and the experiment has a duration — which is exactly the thing summaries drop.

1. The TSC complex acts as a GAP for Rheb, which is how growth-factor and stress signals reach the pathway
2. Rheb contributes to mTORC1 activation, and its GTP-bound state is the form that does it
3. That Rheb is the only determinant of mTORC1 activity
4. Localisation is part of the mechanism rather than a detail drawn on top of it

Answer: C. Several of the foundational experiments in this lesson raised the amount of a protein far above its normal level in order to see its effect. That design is informative about what a protein can do and much weaker evidence about what it normally does — and the studies below are M and A, which marks the design, not the quality.

mTOR regulates memory CD8 T-cell differentiation (2009, Mouse)
mTOR is a key regulator of memory CD8 T-cell differentiation; rapamycin enhances memory responses.
Sample: not stated

1. No lifespan or healthspan endpoint. Side-effect endpoints only; benefit retention is inferred, not tested.
2. Inference from a single exceptional responder; basis of mTOR-inhibitor sensitivity incompletely understood; short drug exposure in some.
3. FDA changed the primary endpoint between phase 2b and phase 3 (symptom-based vs lab-confirmed), complicating comparison; positive biomarker did not translate to…
4. mTOR knockdown does not completely mimic rapamycin treatment.

Answer: D. Its own limitation, as recorded in the Atlas: mTOR knockdown does not completely mimic rapamycin treatment.

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system (2015, Mouse)
Mice given rapamycin every day (2 mg/kg) developed glucose intolerance (the glucose curve was about 71% higher), raised fasting glucose and insulin, and their pancreatic islets released less insulin. The same dose given once every 5 days did not impair…
Sample: 9-11 male C57BL/6J mice per treatment group for glucose tolerance tests; 3-6 mice per group for blood rapamycin concentration; 4-9 mice per group for…

1. Histological evaluation of cataracts was limited to a small number of specimens; site-to-site variation was considerable for spontaneous activity; some observed trends…
2. Inference from rare responders; basis of mTOR-inhibitor sensitivity beyond TSC1/2 loss still incompletely understood.
3. No lifespan or healthspan endpoint. Side-effect endpoints only; benefit retention is inferred, not tested.
4. Specific inhibitors of mTORC2 are unavailable, precluding pharmacological testing.

Answer: C. Its own limitation, as recorded in the Atlas: No lifespan or healthspan endpoint. Side-effect endpoints only; benefit retention is inferred, not tested.

Unphosphorylated 4E-BP1 clamps onto eIF4E and stops it assembling the cap-binding complex. mTORC1 phosphorylates 4E-BP1 to release that grip - so the brake on translation is released, not the accelerator pressed.

1. Established
2. Emerging
3. Contested
4. Open — no answer either way

Answer: A. Curated in the Atlas as consensus established, mechanistic evidence high, human relevance plausible. Scope: Biochemical and cell-culture evidence (in vitro assays, mammalian and mouse cells, plus one review). It establishes the binding switch itself. It does not measure how much translation changes in a…

Keeping 4E-BP active extends lifespan under dietary restriction in flies, by enhancing mitochondrial activity. One of the few places where a single downstream node, not the whole pathway, carries the lifespan effect.

1. Established
2. Emerging
3. Contested
4. Open — no answer either way

Answer: B. Curated in the Atlas as consensus emerging, mechanistic evidence medium, human relevance untested. Scope: Fly only, and only under dietary restriction - the effect was not seen on a full diet.

Unphosphorylated 4E-BP1 clamps onto eIF4E and stops it assembling the cap-binding complex. mTORC1 phosphorylates 4E-BP1 to release that grip - so the brake on translation is released, not the accelerator pressed.

1. MAX2009 — Molecular mechanisms of mTOR-mediated translational control (2009)
2. PEA2009 — Enhancing CD8 T-cell memory by modulating fatty acid metabolism (2009)
3. SAB1995 — Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells (1995)
4. ZID2009 — 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in… (2009)

Answer: A. The Atlas records MAX2009, THO2012, SCH2003 as evidence for this step.

1. activates
2. inhibits

Answer: B. Unphosphorylated 4E-BP1 clamps onto eIF4E and stops it assembling the cap-binding complex. mTORC1 phosphorylates 4E-BP1 to release that grip - so the brake on translation is released, not the accelerator pressed.

1. activates
2. inhibits

Answer: B. Akt phosphorylates TSC2, disabling the complex. Growth-factor signalling works by removing a brake, not by pressing an accelerator.

1. activates
2. inhibits

Answer: B. AMPK also hits mTORC1 directly by phosphorylating Raptor, imposing a metabolic checkpoint independent of TSC.

1. activates
2. inhibits

Answer: A. When energy runs low, AMPK phosphorylates TSC2 and strengthens the brake on Rheb.

Leucine ⊣ Sestrin2 ⊣ GATOR2 ⊣ GATOR1 ⊣ Rag GTPases

Growth hormone / IGF-1 axis → PI3K → Akt/PKB ⊣ TSC1/TSC2 ⊣ Rheb → mTORC1 → S6K1 ⊣ IRS-1 / IRS-2 — 2 of these steps is indirect: it runs through a step this route does not draw.