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Glycogen synthase kinase 3 phosphorylation of different residues in the presence of different factors: Analysis on tau protein

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Abstract

Several peptides derived from microtubule-associated tau protein, have been tested as substrates for glycogen synthase kinase 3 (GSK 3). In the absence of cofactors, GSK 3 can modify serines or threonines followed by prolines. In other cases, a phosphorylation in position +4 is required for the phosphorylation of threonine/serine residues. A third type of substrate can be modified by GSK 3 in the presence of heparin. The comparison of GSK 3 with other kinases suggests some similar features of this kinase with proline-directed protein kinases, such as cdc-2 or mitogen-activated protein kinase (MAP Kinases) and also with casein kinase 2 (CK 2). Thus, all these kinases are specifically inhibited by 5,6-Dichloro-1-β-D-ribofuranosyl)-benzimidazole (DRB). However, heparin is an inhibitor of CK 2 whereas it activates the modification of certain substrates by GSK 3. A possible explanation for the obtained results is that the consensus sequence for GSK 3 phosphorylation is a serine/ threonine adjacent to a proline or other β-turn former residue and that such recognition could be favoured by the presence of adjacent negative charges or the addition of polyanions.

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Abbreviations

GSK 3:

glycogen synthase kinase 3

PDPK:

proline-directed protein kinase

DRB:

5,6-Dichloro-1-β-Dribofuranosyl)benzimidazole

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  1. Centro de Biología Molecular ‘Severo Ochoa’, Universidad Autónoma de Madrid, 28049, Cantoblanco, Madrid, Spain

    Francisco J. Moreno, J. R. Muñoz-Montaño & Jesús Avila

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  1. Francisco J. Moreno
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  2. J. R. Muñoz-Montaño
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  3. Jesús Avila
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Moreno, F.J., Muñoz-Montaño, J.R. & Avila, J. Glycogen synthase kinase 3 phosphorylation of different residues in the presence of different factors: Analysis on tau protein. Mol Cell Biochem 165, 47–54 (1996). https://doi.org/10.1007/BF00229744

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  • DOI: https://doi.org/10.1007/BF00229744

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