Phosphorylation of tau by proline-directed protein kinase (p34cdc2/p58cyclin A) decreases tau-induced microtubule assembly and antibody SMI33 reactivity.
Tau protein was evaluated as a substrate for a proline-directed protein kinase (p34cdc2/p58cyclin A) which recognizes the phosphorylation site motif X-Ser/Thr-Pro-X. The shortest human tau isoform, expressed as a recombinant protein, was phosphorylated to a stoichiometry of 2 mol phosphate/mol tau. Phosphoamino acid analysis revealed phosphorylation of both serine and threonine residues. Phosphorylation of recombinant tau resulted in a decreased ability to induce microtubule assembly but had no effect on the final extent of microtubule formation or on the rate of cold-induced microtubule disassembly. Phosphorylation of tau by the proline-directed protein kinase completely blocked immunoreactivity with antibody SMI33. Phosphorylation did not create the epitopes for the phosphate-dependent antibodies SMI31 or SMI34. Antibody SMI33 recognizes neurofibrillary tangles after treatment with alkaline phosphatase, suggesting that the proline-directed protein kinase may phosphorylate tau at sites that are phosphorylated in Alzheimer's disease.
Scott
C W
CW
Pharmacology Department, ICI Americas Inc., Wilmington, DE 19897-2500.
Vulliet
P R
PR
Caputo
C B
CB
D000595:Amino Acid Sequence; D000906:Antibodies; D000936:Antigen-Antibody Complex; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D016875:tau Proteins / Q000378:metabolism*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D016213:Cyclins; D011994:Recombinant Proteins; D016875:tau Proteins; D016203:CDC2 Protein Kinase