pdk-1
C. elegans
3-phosphoinositide-dependent protein kinase 1
What the model saw
Gene: pdk-1 Organism: Caenorhabditis elegans Known functions: 3-phosphoinositide-dependent protein kinase 1. ATP binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
3-phosphoinositide-dependent protein kinase 1. ATP binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
PDK-1 (3-phosphoinositide-dependent protein kinase 1) is the C. elegans ortholog of mammalian PDK1, a central effector of the insulin/IGF-1 signaling (IIS) pathway. Upon PI3K activation by DAF-2 (insulin/IGF-1 receptor), PDK-1 is recruited to the membrane via its PH domain and phosphorylates AKT-1/AKT-2, which in turn phosphorylates and cytoplasmatically sequesters the FOXO transcription factor DAF-16. DAF-16 nuclear exclusion suppresses expression of stress-resistance, detoxification, and longevity-promoting genes. Reduced IIS signaling (e.g., daf-2 or pdk-1 loss-of-function) is one of the most robust pro-longevity interventions in C. elegans, dramatically extending lifespan in a DAF-16-dependent manner. Therefore, normal PDK-1 activity promotes IIS and opposes longevity by keeping DAF-16 inactive.
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 correctly identified pdk-1 as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: PDK-1 is a key component of the insulin/IGF-1 signaling pathway in C. elegans, phosphorylating AKT-1/AKT-2, which leads to cytoplasmic sequestration of DAF-16 (FOXO), suppressing longevity-promoting genes. Loss-of-function of pdk-1 extends lifespan in a DAF-16-dependent manner, making it anti-longevity. The pathway identification (IIS, DAF-2/PDK-1/AKT/DAF-16 axis) is spot-on.
Raw API responses
solver
{
"reasoning": "PDK-1 (3-phosphoinositide-dependent protein kinase 1) is the C. elegans ortholog of mammalian PDK1, a central effector of the insulin/IGF-1 signaling (IIS) pathway. Upon PI3K activation by DAF-2 (insulin/IGF-1 receptor), PDK-1 is recruited to the membrane via its PH domain and phosphorylates AKT-1/AKT-2, which in turn phosphorylates and cytoplasmatically sequesters the FOXO transcription factor DAF-16. DAF-16 nuclear exclusion suppresses expression of stress-resistance, detoxification, and longevity-promoting genes. Reduced IIS signaling (e.g., daf-2 or pdk-1 loss-of-function) is one of the most robust pro-longevity interventions in C. elegans, dramatically extending lifespan in a DAF-16-dependent manner. Therefore, normal PDK-1 activity promotes IIS and opposes longevity by keeping DAF-16 inactive.",
"confidence": 0.92,
"key_pathways": [
"insulin/IGF-1 signaling (IIS)",
"DAF-2/PDK-1/AKT/DAF-16 axis",
"PI3K-dependent kinase cascade"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified pdk-1 as anti_longevity with high confidence (0.92). The mechanistic reasoning is excellent and accurate: PDK-1 is a key component of the insulin/IGF-1 signaling pathway in C. elegans, phosphorylating AKT-1/AKT-2, which leads to cytoplasmic sequestration of DAF-16 (FOXO), suppressing longevity-promoting genes. Loss-of-function of pdk-1 extends lifespan in a DAF-16-dependent manner, making it anti-longevity. The pathway identification (IIS, DAF-2/PDK-1/AKT/DAF-16 axis) is spot-on.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}