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Specific processing of native and phosphorylated tau protein by proteases
1Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
Biochemical and Biophysical Research Communications
|February 15, 1996
Summary
Protein tau phosphorylation by different kinases alters its susceptibility to proteases. This suggests specific phosphorylation patterns influence tau
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Protein tau is implicated in Alzheimer's disease (AD) pathogenesis.
- Tau phosphorylation by various kinases is a key regulatory mechanism.
Purpose of the Study:
- To investigate how phosphorylation by protein kinase A (PKA) or DNA-dependent protein kinase (DNA-PK) affects tau-3 protease susceptibility.
- To determine if kinase-specific tau phosphorylation alters degradation pathways.
Main Methods:
- Human recombinant tau-3 was phosphorylated using PKA or DNA-PK.
- Phosphorylated tau-3 was incubated with thrombin or a dsDNA-stimulated protease.
- Quantitative degradation was assessed using SDS-PAGE analysis.
Main Results:
- Thrombin degraded DNA-PK-phosphorylated tau-3 faster than native or PKA-phosphorylated tau-3.
- The dsDNA-stimulated protease degraded PKA-phosphorylated tau-3 faster than DNA-PK-phosphorylated tau-3.
- Thrombin degradation patterns differed between DNA-PK-phosphorylated tau-3 and other forms.
Conclusions:
- The site and sequence of tau phosphorylation influence its conformation.
- Altered tau conformation affects its accessibility and reactivity to specific proteases.
- Kinase-dependent tau phosphorylation may modulate disease-related proteolytic events.