Functional Implications of Glycogen Synthase Kinase-3-Mediated Tau Phosphorylation

Table 1

Comparison of phosphorylation sites in human Alzheimer and control brain with recombinant tau phosphorylated by GSK-3 in vitro.

Tau residue number	Alzheimer tau	Control brain tau	GSK-3
Tyr18	A
Ser46	A	•	•
Thr50			•
Ser68	•
Thr69	•		•
Thr71	•
Ser113	•
Thr123	A
Ser131
Thr149			•
Thr153	A		•
Thr175	•		•
Thr181	•	•	•
Ser184	•		•
Ser185	•
Ser191	•
Ser195			•
Tyr197	•
Ser198	•	•	•
Ser199	•	•	•
Ser202	•	•	•
Thr205	A	•	•
Ser208	•
Ser210	•		•
Thr212	•	•	•
Ser214	•		•
Thr217	•	•	•
Thr220			•
Thr231	•	•	•
Ser235	•	•	•
Ser237	•		•
Ser238	•
Ser241			•
Thr245			•
Ser258	•		•
Ser262	•		•
Ser285			•
Ser289	•		•
Ser305			•
Ser324			•
Ser352			•
Ser356	•		•
Thr373			•
Tyr394	•
Ser396	•	•	•
Ser400	•	•	•
Thr403	•
Ser404	•	•	•
Ser409	•		•
Ser412	•	**
Ser413	•	**	•
Thr414	*	**
Ser416	A*	•
Ser422	•
Thr427	•
Ser433	•
Ser435	•

Numbering of residues refers to 2N4R human tau, the largest isoform present in the human CNS.
• indicates tau phosphorylation sites identified by direct means.
A indicates tau phosphorylation sites identified using phospho-specific tau antibodies.
* indicates that one of the two closely spaced phosphorylation sites indicated (Thr414, Ser416) is phosphorylated in tau from AD brain.
** indicates that two of the three closely spaced phosphorylation sites indicated (Ser412, Ser413, Thr414) are phosphorylated in tau from control human brain.