Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38δ at Thr50 promotes microtubule assembly

• DOI: 10.1242/jcs.01655
• Publication Date: 2005-01-05T02:33:00Z
• Authors: Carmen Feijoo; David G. Campbell; Ross Jakes; Michel Goedert; Ana Cuenda
• Keywords: Microtubule-associated protein

Phosphorylation regulates both normal and pathological Tau functioning. This microtubule-associated protein plays a role in the organization integrity of neuronal cytoskeleton under conditions becomes hyperphosphorylated aggregated number neurodegenerative diseases referred to as tauopathies. In this study, we identify compare residues human phosphorylated vitro by all four p38 MAPK isoforms, study regulation phosphorylation Thr50, where MAPKs are active cells. Through biochemical analysis, loss function studies analysis endogenous overexpressed proteins, show that SAPK4/p38δ is major kinase phosphorylating Thr50 Tau, when cells exposed osmotic stress. We also mutation glutamic acid, which mimics phosphorylation, increases ability promote tubulin polymerisation vivo. Moreover, filamentous from Alzheimer's disease brain. These findings suggest for adaptative response neurons stress indicate and/or SAPK3/p38δ may contribute hyperphosphorylation