What question did this study set out to answer?

Determine which protein kinase A phosphorylation sites on human tau protein are essential for high-affinity binding to 14-3-3ζ.

August 3, 2009FEBS Letters

Phosphorylation of more than one site is required for tight interaction of human tau protein with 14‐3‐3ζ

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Authors

NSNikolai N. SluchankoA N Bach Institute of Biochemistry ASAlim S. Seit‐NebiTriLink BioTechnologies (United States)NGNikolai B. GusevLomonosov Moscow State University

Discussion

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Implication

In vitro mutational analysis reveals multi-site phosphorylation requirements for 14-3-3ζ binding in human tau protein, suggesting a mechanism regulating pathological filament formation.

Key Points

Determine which protein kinase A phosphorylation sites on human tau protein are essential for high-affinity binding to 14-3-3ζ.
Sequentially mutated serine residues phosphorylated by protein kinase A (PKA) to alanine in the shortest isoform of human tau (tau3).
Assayed binding interactions between phosphorylated wild-type or mutated tau3 isoforms and 14-3-3ζ.
Single substitution S156A caused a slight reduction in binding between phosphorylated tau3 and 14-3-3ζ.
Double alanine substitutions S156A/S267A and particularly S156A/S235A strongly inhibited tau3 interaction with 14-3-3ζ.
Demonstrated that cooperative phosphorylation at two sites across the proline-rich domain and pseudo-repeats of tau3 governs 14-3-3 binding and may modulate filament formation.

Cite This Study

Sluchanko et al. (2009) studied this question.

synapsesocial.com/papers/6a8736733a1d8ec5fdd3e739 https://doi.org/10.1016/j.febslet.2009.07.043

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August 3, 2009FEBS Letters

Phosphorylation of more than one site is required for tight interaction of human tau protein with 14‐3‐3ζ

View Full Paper

Ask AI

Bookmark

Authors

NSNikolai N. SluchankoA N Bach Institute of Biochemistry ASAlim S. Seit‐NebiTriLink BioTechnologies (United States)NGNikolai B. GusevLomonosov Moscow State University

Discussion

Member takes

Implication

In vitro mutational analysis reveals multi-site phosphorylation requirements for 14-3-3ζ binding in human tau protein, suggesting a mechanism regulating pathological filament formation.

Key Points

Determine which protein kinase A phosphorylation sites on human tau protein are essential for high-affinity binding to 14-3-3ζ.
Sequentially mutated serine residues phosphorylated by protein kinase A (PKA) to alanine in the shortest isoform of human tau (tau3).
Assayed binding interactions between phosphorylated wild-type or mutated tau3 isoforms and 14-3-3ζ.
Single substitution S156A caused a slight reduction in binding between phosphorylated tau3 and 14-3-3ζ.
Double alanine substitutions S156A/S267A and particularly S156A/S235A strongly inhibited tau3 interaction with 14-3-3ζ.
Demonstrated that cooperative phosphorylation at two sites across the proline-rich domain and pseudo-repeats of tau3 governs 14-3-3 binding and may modulate filament formation.

Cite This Study

Sluchanko et al. (2009) studied this question.

synapsesocial.com/papers/6a8736733a1d8ec5fdd3e739 https://doi.org/10.1016/j.febslet.2009.07.043

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