mek-2
C. elegans
Dual specificity mitogen-activated protein kinase kinase mek-2
What the model saw
Gene: mek-2 Organism: Caenorhabditis elegans Known functions: Dual specificity mitogen-activated protein kinase kinase mek-2. ATP binding. MAP kinase kinase activity. protein kinase activity. protein serine kinase activity. protein serine/threonine/tyrosine kinase activity. protein tyrosine kinase activity. scaffold protein binding.
View unredacted entry
Dual specificity mitogen-activated protein kinase kinase mek-2. ATP binding. MAP kinase kinase activity. protein kinase activity. protein serine kinase activity. protein serine/threonine/tyrosine kinase activity. protein tyrosine kinase activity. scaffold protein binding.
Solver output
MEK-2 is the C. elegans ortholog of MEK1/2 (MAP2K1/2), a dual-specificity MAP kinase kinase that phosphorylates and activates MPK-1/ERK in the canonical RAS-RAF-MEK-ERK MAPK cascade. In C. elegans, this pathway (LET-60 RAS → LIN-45 RAF → MEK-2 → MPK-1) promotes cell proliferation and differentiation signals that are generally antagonistic to longevity-promoting pathways. Hyperactivation of RAS-MAPK signaling is well-established to oppose longevity by promoting growth and proliferation at the expense of stress resistance and maintenance programs. The MEK-ERK axis intersects with and can antagonize DAF-16/FOXO activity, a central pro-longevity transcription factor downstream of the insulin/IGF-1 signaling pathway. Additionally, elevated MAPK signaling contributes to cellular senescence and chronic inflammation in aging contexts. Loss-of-function in this pathway in C. elegans is associated with extended lifespan, consistent with MEK-2's normal function being anti-longevity.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted anti_longevity for mek-2, but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect logic: it assumes that because RAS-MAPK signaling promotes growth/proliferation, it must be anti-longevity in C. elegans. However, mek-2 is actually pro-longevity in C. elegans. The model's mechanistic reasoning about DAF-16/FOXO antagonism and RAS-MAPK being anti-longevity is the standard mammalian/cancer biology framing, which doesn't correctly capture the role of mek-2 in C. elegans longevity. The model was fairly confident (0.72) in its wrong answer. The actual pro-longevity role of mek-2 in C. elegans may relate to its involvement in stress responses or other context-specific functions that differ from the simple growth-promotion narrative the model applied.
Raw API responses
solver
{
"reasoning": "MEK-2 is the C. elegans ortholog of MEK1/2 (MAP2K1/2), a dual-specificity MAP kinase kinase that phosphorylates and activates MPK-1/ERK in the canonical RAS-RAF-MEK-ERK MAPK cascade. In C. elegans, this pathway (LET-60 RAS → LIN-45 RAF → MEK-2 → MPK-1) promotes cell proliferation and differentiation signals that are generally antagonistic to longevity-promoting pathways. Hyperactivation of RAS-MAPK signaling is well-established to oppose longevity by promoting growth and proliferation at the expense of stress resistance and maintenance programs. The MEK-ERK axis intersects with and can antagonize DAF-16/FOXO activity, a central pro-longevity transcription factor downstream of the insulin/IGF-1 signaling pathway. Additionally, elevated MAPK signaling contributes to cellular senescence and chronic inflammation in aging contexts. Loss-of-function in this pathway in C. elegans is associated with extended lifespan, consistent with MEK-2's normal function being anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"RAS-RAF-MEK-ERK MAPK signaling cascade",
"Insulin/IGF-1 signaling and DAF-16/FOXO antagonism",
"Cellular proliferation and growth signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted anti_longevity for mek-2, but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect logic: it assumes that because RAS-MAPK signaling promotes growth/proliferation, it must be anti-longevity in C. elegans. However, mek-2 is actually pro-longevity in C. elegans. The model's mechanistic reasoning about DAF-16/FOXO antagonism and RAS-MAPK being anti-longevity is the standard mammalian/cancer biology framing, which doesn't correctly capture the role of mek-2 in C. elegans longevity. The model was fairly confident (0.72) in its wrong answer. The actual pro-longevity role of mek-2 in C. elegans may relate to its involvement in stress responses or other context-specific functions that differ from the simple growth-promotion narrative the model applied.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}