MAPK / Ras Signaling Cascade Tournament
Two onboarding diagrams orient you in signal transduction. Then eight MCAT-DoK quiz rounds: Raf as the Ras-binding MAP3K, BRAF V600E in melanoma + vemurafenib resistance, the canonical Grb2-SOS-Ras-Raf-MEK-ERK choreography, the three-tier kinase amplifier, scaffolds + DUSPs for negative feedback, and NF1 / neurofibromatosis as the textbook RASopathy.
Where the MAPK family signaling cascades fits in Signal Transduction
The Ras-Raf-MEK-ERK MAPK cascade is the prototype mitogenic signaling module: a three-tier kinase amplifier downstream of receptor tyrosine kinases. Mutations at every node drive cancer (KRAS, BRAF V600E, NF1 RASopathies). Click the highlighted MAPK family signaling cascades box to enter the tournament.
Click the highlighted MAPK family signaling cascades 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 MAPK inside signal transduction on the live Reactome map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways MAPK figure before you start answering.
Fill in the Blank
Recall Raf as the Ras-GTP-binding MAP3K that activates MEK1/2.
Disruptor
Predict why BRAF V600E melanomas respond to vemurafenib but reactivate the same MEK-ERK output.
Sequence Ordering
Trace the canonical RTK -> Grb2 -> SOS -> Ras -> Raf -> MEK -> ERK -> nuclear-target sequence.
Match the Pairs
Pair each component (Ras, Grb2, Raf, MEK, ERK, DUSPs, vemurafenib) with its precise role.
Numeric Input
Recognize the three-tier MAP3K -> MAP2K -> MAPK architecture.
Select All That Apply
Identify TRUE facts about Ras GTPase, oncogenic mutations, scaffolds, and ERK shuttling.
Odd One Out
Distinguish Smad2/3 (TGF-β pathway) from Grb2/SOS/Raf (MAPK pathway).
NF1 RASopathy Disruptor
Recognize neurofibromin loss as the textbook hereditary RASopathy.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
MAPK signaling in 60 seconds
The Ras-Raf-MEK-ERK MAPK cascade is the prototype three-tier kinase module: MAP3K (Raf) -> MAP2K (MEK) -> MAPK (ERK). Each tier amplifies + adds specificity through scaffolds (KSR) and feedback phosphatases (DUSPs).
Activation flow: RTK -> Grb2 -> SOS -> Ras-GTP -> Raf -> MEK -> ERK -> nucleus. Termination: Ras intrinsic GTPase + RasGAPs + DUSPs. Two parallel MAPK modules also exist (JNK for stress + AP-1; p38 for inflammation + stress).
Cancer hits the pathway at every node: KRAS mutations (~30% of all tumors; pancreatic, colorectal, lung), BRAF V600E (melanoma; ~50%), NF1 RasGAP loss (neurofibromatosis), and rare MEK-activating mutations.
Pharmacology: vemurafenib + dabrafenib (BRAF V600E inhibitors), trametinib (MEK inhibitor). Combination therapy delays resistance. MEK inhibitors are also FDA-approved for NF1-associated plexiform neurofibromas (selumetinib).
FAQ
What is a 'RASopathy'?
A genetic syndrome caused by germline mutations in Ras-MAPK pathway components. Examples: NF1 (neurofibromin), Noonan (PTPN11/SHP2), Costello (HRAS), cardiofaciocutaneous (BRAF, MAP2K1/2). They share short stature, characteristic faces, cardiac defects.
Why is BRAF + MEK combination therapy more effective than BRAF inhibitor alone?
Resistance to BRAF inhibitors typically arises through reactivation of the same MEK-ERK output (CRAF dimerization, NRAS mutations, MEK-activating mutations). Adding a MEK inhibitor blocks the next downstream node, delaying these resistance routes.
Is Raf a tyrosine kinase?
No. Raf is a serine/threonine kinase that phosphorylates MEK on Ser/Thr residues. MEK is a dual-specificity kinase (Ser/Thr + Tyr) that activates ERK by phosphorylating both a Thr and a Tyr in ERK's activation loop.
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
Where insulin's RTK uses IRS + PI3K-Akt instead of the canonical Grb2-Ras-MAPK route.
GPCRs vs. RTKs - the two great families of cell-surface signaling architecture.
Overview diagram: Reactome Pathway R-HSA-162582, licensed CC BY 4.0.