Fig. 3.

Serines (S) 129, 214, 352, and 409 on tau represent putative PKA phosphorylation targets. Serine and threonine phosphorylation sites for nonproline-directed kinases have been identified in hTau40. Nonproline-directed kinase consensus sites are normally localized inside or between the microtubule-binding repeat domains, R1–R4. Among them, putative PKA consensus sites, with specific R(R)XSX motifs, have been found at serines 129, 214, 352, and 409 via gene alignment analysis. Other kinase phosphorylation sites, e.g., the specific KXGS motif for microtubule affinity-regulating kinase (MARK), have been identified at serines 262 and 356. Multiple phosphorylation sites for proline-directed kinase sites (TP, SP) are indicated at the NH₂ and COOH termini of tau, outside of the R1–R4 domains.