Hyperphosphorylation is a pathological process in which excessive phosphate groups are added to a protein, typically at serine, threonine, or tyrosine residues. It is often due to an imbalance between kinase and phosphatase activities.
Definition
Abnormal increase in phosphorylation beyond physiological levels.
Leads to altered protein structure, function, and interactions.
Often irreversible in pathological states.
Mechanism
Protein kinases (e.g., CDK5, GSK-3β, AMPK) add phosphate groups.
Protein phosphatases (e.g., PP2A) remove them.
In disease states, kinase activity is upregulated or phosphatase activity is suppressed.
Pathological Consequences
Protein misfolding
Loss of normal function
Aggregation and toxicity
Clinical Relevance
Alzheimer’s Disease
Tau hyperphosphorylation → detachment from microtubules
Aggregation into neurofibrillary tangles
Driven by overactive CDK5, GSK-3β, and suppressed PP2A
Cancer
Oncogenic signaling via hyperphosphorylated proteins