Signal transduction 4 (Nutrient and Energy Sensing Signalling)

… kinase regulates processes such as translation and transcription in response to … status and signals from … …. receptors

TOR, nutritional, cell surface

… … factors and … proteins can be regulated by … by TOR kinase, which affects the rate of translation of mRNAs and hence the overall rate of protein synthesis

translation initiation, ribosomal, phosphorylation

what is the mammalian version of TOR?

mTOR

mammalian cells contain two distinct mTOR-containing complexes referred to as … and …

mTORC1 and mTORC2

the mTORC1 is composed of …, … and … (core components)

mTOR, Raptor and mLST8

mTORC1 controls protein synthesis by phosphorylating … (a kinase) and … which are two proteins which regulate translation - this leads to an INCREASE in protein synthesis

S6K1/2 and 4E-BP1

function of S6K1/2 (through which it increases the rate of protein synthesis)

phosphorylates ribosomal proteins

function of 4E-BP1 (thorugh which it inhibits protein synthesis)

inhibits interaction of a key translation initiation factor with mRNA

respectively, are S6K1/2 and 4E-BP1 activated or suppressed by phosphorylation?

activated, suppressed

… activity is regulated by Rheb (a small G protein)

mTOR

Rheb activity is controlled by …/… which is a Rheb-GAP (… … …)

TSC1/TSC2, GTPase activating protein

TSC1/TSC2 complex increases Rheb’s low intrinsic GTPase activity stimulating conversion of active …-… to inactive …-…

Rheb-GTP, Rheb-GDP

in response to insulin, … inhibits TSC2 (through phosphorylation), allowing Rheb-GTP to accumulate and activate mTORC1

Akt

glucose, oxygen and other factors influencing energy status affect levels of AMP, which activates …, which exerts inhibitory effects on mTORC1 though activation of … and inhibition of … (through phosphorylation of a key … residue)

AMPK, TSC2, Raptor, serine

exercise increases levels of AMP and thus … AMPK (activates/inhibits)

activates

intracellular amino acids are sensed by mTORC1 though a pathway affecting the … …

Rag GTPases

name the two Rag GTPases (also add whether they are rich in GTP or GDP when amino acids are high)

Rag A/B (GTP) and Rag C/D (GDP)

when mTOR signalling pathway is active, processes such as … … and … … are active and upregulated

mRNA translation and cell proliferation

in a nutshell, mTOR controls cell …, … and … in response to … availability, … levels and … factors, acting as a sensor for activating … processes and inhibiting … processes

growth, proliferation, metabolism, nutrient, energy, growth, anabolic, catabolic

all conserved components of TORC1 complex can be found in … (organisms besides animals)

plants

fungal ortholog of AMPK

SnF1

plant ortholog of AMPK

SnRK1

TOR essentially connects … sensing to … … machinery

nutrient, cell growth

signalling sugar molecule in plants which functions as a regulator of energy status

trehalose 6 phosphate

does trehalose-6-phosphate activate or inhibit SnRK1 in plants?

inhibit

does SnRK1 activate or inhibit growth response in plants?

inhibit

do low sugar conditions (low trehalose-6-phosphate levels) activate or inhibit SnRK1 in plants?

activate

which two sugars repress SnRK1 activity?

glucose 6 phosphate and trehalose 6 phosphate

what allosterically regulates mammalian AMPK the same way glucose and trehalose 6 phosphate regulate SnRK1?

AMP/ATP ratio

can glucose-6-phosphate and trehalose-6-phosphate directly promote TORC1 activity?

yes