Evidences p(HGNC:MAPT, pmod(Ph, Tyr, 18)) to p(HGNC:SYK)

We found that tau phosphorylation at Y18 is significantly increased in neurons that are also immunopositive for pSyk (Fig. 10d, p < 0.05) which is consistent with previous data showing that in vitro Syk can phosphorylates tau at Y18.

Altogether, these data suggest that only certain pathogenic forms of tau (MC1, Y18) promote Syk activation, whereas Syk activation appears to directly in- duce tau phosphorylation at Y18 and to indirectly regulate tau phosphorylation at multiple epitopes (S396/404, S202) as well as tau misfolding (MC1, TOC1).

We found an increase in Syk activation in DNs surrounding A β deposits as well as in neurons displaying an accumu- lation of phosphorylated Tau at Y18 and elevated levels of MC1 pathogenic tau conformers in AD brain sections whereas only weak immunoreactivity for pSyk was ob- served in brain sections from a non-demented control (Figs. 15, 16 and 17).

Syk has been shown to mediate the phosphorylation of Tau at Tyr-18 (56).

Interestingly, Syk up- regulation in SH-SY5Y cells leads to a significant in- crease (1.7-fold) in phosphorylated tau at Y18 (Fig. 14c, p < 0.01) and at S396/404 (Fig. 14d, 3-fold, p < 0.0001) compared to control cells.

In addition, tau can be phosphorylated by tyrosine kinases such as the SRC family members LCK, SYK and FYN at Tyr18, and the ABL family members ARG and ABL1 at Tyr394 (REF. 45).

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.