sgk-1
C. elegans
Serine/threonine-protein kinase sgk-1
What the model saw
Gene: sgk-1 Organism: Caenorhabditis elegans Known functions: Serine/threonine-protein kinase sgk-1. ATP binding. phosphatidylinositol-3,4,5-trisphosphate binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Serine/threonine-protein kinase sgk-1. ATP binding. phosphatidylinositol-3,4,5-trisphosphate binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
SGK-1 (serum- and glucocorticoid-induced kinase 1) is a downstream effector of the PI3K/PDK-1 signaling axis in C. elegans, activated by PIP3 binding — the same lipid second messenger that activates AKT-1/AKT-2. As a serine/threonine kinase downstream of insulin/IGF-1 signaling (IIS), SGK-1 phosphorylates and inhibits the FOXO transcription factor DAF-16, preventing its nuclear translocation and suppression of pro-aging gene programs. Reduced IIS — including loss of sgk-1 function — extends lifespan in C. elegans by allowing DAF-16/FOXO nuclear activity, upregulating stress resistance and longevity genes. Thus, the normal (active) function of SGK-1 promotes aging by dampening DAF-16-mediated longevity pathways. This places sgk-1 squarely within the deregulated nutrient-sensing hallmark, specifically the insulin/IGF-1 → PI3K → PIP3 → SGK-1 → DAF-16 axis.
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 predicted anti_longevity for sgk-1 in C. elegans with high confidence (0.82). The mechanistic reasoning is accurate and detailed: SGK-1 is indeed a downstream effector of the insulin/IGF-1 signaling pathway, activated by PIP3, and functions to phosphorylate and inhibit DAF-16/FOXO, thereby promoting aging. Loss of sgk-1 extends lifespan by allowing DAF-16 nuclear activity. The pathway description (IIS → PI3K → PIP3 → SGK-1 → DAF-16) is correct. The classification as "deregulated_nutrient_sensing" is appropriate. Overall, this is an excellent prediction with correct answer and correct mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "SGK-1 (serum- and glucocorticoid-induced kinase 1) is a downstream effector of the PI3K/PDK-1 signaling axis in C. elegans, activated by PIP3 binding — the same lipid second messenger that activates AKT-1/AKT-2. As a serine/threonine kinase downstream of insulin/IGF-1 signaling (IIS), SGK-1 phosphorylates and inhibits the FOXO transcription factor DAF-16, preventing its nuclear translocation and suppression of pro-aging gene programs. Reduced IIS — including loss of sgk-1 function — extends lifespan in C. elegans by allowing DAF-16/FOXO nuclear activity, upregulating stress resistance and longevity genes. Thus, the normal (active) function of SGK-1 promotes aging by dampening DAF-16-mediated longevity pathways. This places sgk-1 squarely within the deregulated nutrient-sensing hallmark, specifically the insulin/IGF-1 → PI3K → PIP3 → SGK-1 → DAF-16 axis.",
"confidence": 0.82,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"PI3K-PIP3-PDK-1-SGK-1 axis",
"DAF-16/FOXO transcription factor regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for sgk-1 in C. elegans with high confidence (0.82). The mechanistic reasoning is accurate and detailed: SGK-1 is indeed a downstream effector of the insulin/IGF-1 signaling pathway, activated by PIP3, and functions to phosphorylate and inhibit DAF-16/FOXO, thereby promoting aging. Loss of sgk-1 extends lifespan by allowing DAF-16 nuclear activity. The pathway description (IIS → PI3K → PIP3 → SGK-1 → DAF-16) is correct. The classification as \"deregulated_nutrient_sensing\" is appropriate. Overall, this is an excellent prediction with correct answer and correct mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}