GPCR Signaling Tournament
Two onboarding diagrams orient you in signal transduction. Then eight MCAT-DoK quiz rounds: adenylate cyclase as Gαs effector, cholera toxin's Gαs lock, the canonical 7-step GPCR cascade, Gα family-effector matching, the 7-transmembrane architecture, β-arrestin desensitization, and how insulin's RTK pathway differs from a GPCR.
Where the Signaling by GPCR fits in Signal transduction overview
GPCRs are the largest receptor superfamily in humans (~800 genes). Seven transmembrane helices, three Gα families (Gs, Gi, Gq), and second messengers (cAMP, IP3, DAG, Ca2+) build out most of the hormonal + neurotransmitter pharmacology you have to know. Click the highlighted Signaling by GPCR box to enter the tournament.
Click the highlighted Signaling by GPCR box to continue.
What this tournament tests
Each task maps to a distinct MCAT cognitive demand. The first two orient you in the broader topology; the next eight test the high-yield mechanism, regulation, sequence and quantitative reasoning that consistently appear on test day.
The Bigger Picture
Anchor GPCR signaling inside the broader signal-transduction landscape on the live Reactome map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways G-protein figure before you start answering.
Fill in the Blank
Recall adenylate cyclase as the Gαs effector that makes cAMP -> PKA.
Disruptor
Predict how cholera toxin ADP-ribosylates Gαs to lock cAMP high in intestinal cells.
Sequence Ordering
Order ligand binding -> GEF activity -> GTP exchange -> Gαs-AC -> cAMP -> PKA -> CREB -> termination.
Match the Pairs
Pair each Gα family (Gαs, Gαi, Gαq, Gα12/13, Gβγ) with its main effector and a representative receptor.
Numeric Input
Recall the canonical 7-transmembrane architecture of GPCRs.
Select All That Apply
Identify TRUE facts about GPCRs as GEFs, β-arrestin signaling, AKAPs, and Gβγ active signaling.
Odd One Out
Distinguish insulin (RTK) from albuterol / atropine / losartan (all GPCR-targeting).
Tachyphylaxis Disruptor
Predict why chronic β-agonist use loses potency via GRK + arrestin internalization.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
GPCR signaling in 60 seconds
A GPCR is a 7-transmembrane receptor that activates heterotrimeric G proteins (αβγ). Ligand binding triggers a conformational change that lets the receptor act as a GEF for Gα: GDP -> GTP exchange. Gα-GTP separates from Gβγ and both can signal.
Three big Gα families: Gαs (-> ↑adenylate cyclase, ↑cAMP, PKA), Gαi (-> ↓adenylate cyclase, ↓cAMP), Gαq (-> phospholipase C, IP3 + DAG, Ca2+ + PKC). Knowing which Gα each receptor couples to is the master key for autonomic and hormonal pharmacology.
Two textbook toxins: cholera toxin ADP-ribosylates Gαs (locks ON, cAMP up, watery diarrhea) and pertussis toxin ADP-ribosylates Gαi (locks OFF, cAMP also up because the brake is broken). Both produce hypersecretion - in different organs.
Termination + desensitization: Gα has intrinsic GTPase activity (RGS proteins help); PDE breaks down cAMP;GRK + β-arrestin phosphorylate the receptor and promote endocytosis -> the molecular basis of β-blocker tolerance and opioid tachyphylaxis.
FAQ
Why does cholera produce diarrhea but pertussis produce coughing?
Same molecular trick (ADP-ribosylation of a G protein), different tissue targets. Cholera toxin enters intestinal epithelial cells and locks Gαs -> sustained cAMP -> CFTR-driven Cl- and water secretion -> watery diarrhea. Pertussis toxin enters airway epithelium and locks Gαi off, with similarly elevated cAMP plus altered host immunity that drives the paroxysmal cough.
How is signaling by insulin different from signaling by adrenaline at β2?
Insulin uses a RECEPTOR TYROSINE KINASE - dimerization + autophosphorylation -> SH2 recruitment -> Ras/MAPK or PI3K/Akt cascades. Adrenaline at β2 uses a GPCR -> Gαs -> cAMP -> PKA. Different architecture, different second messengers, different downstream substrates.
What is biased agonism?
Some ligands preferentially activate either G-protein signaling or β-arrestin signaling at the same GPCR. Biased agonists at the µ-opioid receptor (in development) try to retain analgesia (G-protein) while reducing β-arrestin-mediated respiratory depression - a hot area of GPCR drug design.
Do I need an account to play?
No. The tournament is fully public. You get a randomized handle and your score posts to the public leaderboard at the bottom of this page.
Keep going
Death-receptor signaling: Fas / FADD / caspase-8 - a different receptor architecture, but parallel logic.
Where mitogen GPCR + RTK signaling converge - on cyclin D and the G1/S restriction point.
Overview diagram: Reactome Pathway R-HSA-162582, licensed CC BY 4.0.