Glycogen synthase kinase 3 phosphorylation of different residues in the presence of different factors: analysis on tau protein.
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-(beta-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 beta-turn former residue and that such recognition could be favoured by the presence of adjacent negative charges or the addition of polyanions.
Moreno
F J
FJ
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Muñoz-Montaño
J R
JR
Avila
J
J
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D047390:Casein Kinase II; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006493:Heparin / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D013912:Threonine / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D010455:Peptides; D016875:tau Proteins; D013912:Threonine; D012694:Serine; D004004:Dichlororibofuranosylbenzimidazole; D006493:Heparin; D011392:Proline; D011494:Protein Kinases; D038341:Glycogen Synthase Kinases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D038362:Glycogen Synthase Kinase 3