mpk-1
C. elegans
Mitogen-activated protein kinase mpk-1
What the model saw
Gene: mpk-1 Organism: Caenorhabditis elegans Known functions: Mitogen-activated protein kinase mpk-1. ATP binding. MAP kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Mitogen-activated protein kinase mpk-1. ATP binding. MAP kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
mpk-1 is the C. elegans ortholog of ERK (extracellular signal-regulated kinase), the terminal MAP kinase in the RAS/MAPK signaling cascade. In C. elegans, the RAS-ERK/mpk-1 pathway is a key growth and proliferation-promoting axis that antagonizes the DAF-16/FOXO transcription factor, a central pro-longevity effector downstream of reduced insulin/IGF-1 signaling. Activation of mpk-1 promotes somatic and germline growth programs that are generally associated with shortened lifespan, and hyperactivation of RAS-MAPK signaling reduces longevity in multiple model organisms. Furthermore, mpk-1 activity in the germline promotes proliferation at the expense of longevity signals; loss of the germline extends lifespan in a manner partly dependent on reduced mpk-1 activity. Its serine/threonine kinase activity phosphorylates downstream targets that suppress stress resistance and pro-longevity transcriptional programs, placing it as an anti-longevity factor within the nutrient/growth sensing network.
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 mpk-1 as anti_longevity with 0.78 confidence, but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect narrative: it frames mpk-1/ERK as a growth-promoting, DAF-16-antagonizing factor that shortens lifespan. In reality, mpk-1 in C. elegans has pro-longevity roles - for example, mpk-1 activity is required for the lifespan extension seen in germline-less animals (glp-1 mutants), and it plays roles in stress responses that promote longevity. The model's reasoning about germline proliferation is actually partially inverted - mpk-1 activity in the context of germline ablation promotes longevity rather than reducing it. The model was confidently wrong in both the final answer and the mechanistic explanation.
Raw API responses
solver
{
"reasoning": "mpk-1 is the C. elegans ortholog of ERK (extracellular signal-regulated kinase), the terminal MAP kinase in the RAS/MAPK signaling cascade. In C. elegans, the RAS-ERK/mpk-1 pathway is a key growth and proliferation-promoting axis that antagonizes the DAF-16/FOXO transcription factor, a central pro-longevity effector downstream of reduced insulin/IGF-1 signaling. Activation of mpk-1 promotes somatic and germline growth programs that are generally associated with shortened lifespan, and hyperactivation of RAS-MAPK signaling reduces longevity in multiple model organisms. Furthermore, mpk-1 activity in the germline promotes proliferation at the expense of longevity signals; loss of the germline extends lifespan in a manner partly dependent on reduced mpk-1 activity. Its serine/threonine kinase activity phosphorylates downstream targets that suppress stress resistance and pro-longevity transcriptional programs, placing it as an anti-longevity factor within the nutrient/growth sensing network.",
"confidence": 0.78,
"key_pathways": [
"RAS/MAPK (ERK) signaling",
"Insulin/IGF-1 signaling - DAF-16/FOXO antagonism",
"Germline proliferation signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted mpk-1 as anti_longevity with 0.78 confidence, but the ground truth is pro_longevity. The model's reasoning follows a plausible but incorrect narrative: it frames mpk-1/ERK as a growth-promoting, DAF-16-antagonizing factor that shortens lifespan. In reality, mpk-1 in C. elegans has pro-longevity roles - for example, mpk-1 activity is required for the lifespan extension seen in germline-less animals (glp-1 mutants), and it plays roles in stress responses that promote longevity. The model's reasoning about germline proliferation is actually partially inverted - mpk-1 activity in the context of germline ablation promotes longevity rather than reducing it. The model was confidently wrong in both the final answer and the mechanistic explanation.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}