gsk3
S. pombe
serine/threonine protein kinase Gsk3
What the model saw
Gene: gsk3 Organism: Schizosaccharomyces pombe Known functions: serine/threonine protein kinase Gsk3. ATP binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. protein serine/threonine/tyrosine kinase activity. protein tyrosine kinase activity.
View unredacted entry
serine/threonine protein kinase Gsk3. ATP binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. protein serine/threonine/tyrosine kinase activity. protein tyrosine kinase activity.
Solver output
GSK3 (Glycogen Synthase Kinase 3) is a conserved serine/threonine/tyrosine kinase that acts as a central node in nutrient-sensing and growth signaling networks. In multiple organisms, GSK3 orthologs phosphorylate and inhibit anabolic targets downstream of insulin/IGF-1 and TOR signaling, thereby acting as a brake on growth-promoting pathways. Inhibition of GSK3 activity (e.g., by Akt/PKB downstream of insulin signaling) promotes cell growth and proliferation, while active GSK3 suppresses these pathways and can promote stress resistance and autophagy. In S. pombe, Gsk3 is expected to similarly restrain nutrient-driven anabolic signaling; its kinase activity would phosphorylate substrates that limit TOR-dependent growth, analogous to the pro-longevity role seen when insulin/TOR signaling is attenuated. Additionally, GSK3 phosphorylates and destabilizes pro-growth transcription factors, further aligning its activity with longevity-promoting restraint of nutrient sensing. However, context-dependency (GSK3 can also promote senescence in some settings) introduces some uncertainty.
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 pro_longevity but the ground truth is anti_longevity. The model's reasoning about GSK3 being a "brake on growth-promoting pathways" and thus pro-longevity is flawed. In S. pombe, gsk3 is anti-longevity, meaning its activity shortens lifespan (or its deletion extends lifespan). The model confused the direction: while GSK3 does phosphorylate and inhibit anabolic targets, in the context of aging in S. pombe, GSK3 activity is detrimental to longevity. The model's mechanistic reasoning about nutrient sensing is partially relevant but leads to the wrong conclusion. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanistic interpretation as applied to this organism.
Raw API responses
solver
{
"reasoning": "GSK3 (Glycogen Synthase Kinase 3) is a conserved serine/threonine/tyrosine kinase that acts as a central node in nutrient-sensing and growth signaling networks. In multiple organisms, GSK3 orthologs phosphorylate and inhibit anabolic targets downstream of insulin/IGF-1 and TOR signaling, thereby acting as a brake on growth-promoting pathways. Inhibition of GSK3 activity (e.g., by Akt/PKB downstream of insulin signaling) promotes cell growth and proliferation, while active GSK3 suppresses these pathways and can promote stress resistance and autophagy. In S. pombe, Gsk3 is expected to similarly restrain nutrient-driven anabolic signaling; its kinase activity would phosphorylate substrates that limit TOR-dependent growth, analogous to the pro-longevity role seen when insulin/TOR signaling is attenuated. Additionally, GSK3 phosphorylates and destabilizes pro-growth transcription factors, further aligning its activity with longevity-promoting restraint of nutrient sensing. However, context-dependency (GSK3 can also promote senescence in some settings) introduces some uncertainty.",
"confidence": 0.62,
"key_pathways": [
"insulin/IGF-1 - TOR nutrient sensing pathway",
"GSK3-mediated phosphorylation of anabolic substrates",
"stress response and autophagy regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about GSK3 being a \"brake on growth-promoting pathways\" and thus pro-longevity is flawed. In S. pombe, gsk3 is anti-longevity, meaning its activity shortens lifespan (or its deletion extends lifespan). The model confused the direction: while GSK3 does phosphorylate and inhibit anabolic targets, in the context of aging in S. pombe, GSK3 activity is detrimental to longevity. The model's mechanistic reasoning about nutrient sensing is partially relevant but leads to the wrong conclusion. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanistic interpretation as applied to this organism.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}