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Previous work has established that the phosphorylation\u2010dependent anti\u2010tau antibody AT100 is a specific marker for filamentous tau in adult human brain. Here we have identified protein kinases that generate the AT100 epitope<jats:italic>in vitro<\/jats:italic>and have used them, in conjunction with site\u2010directed mutagenesis of tau, to map the epitope. We show that the sequential phosphorylation of recombinant tau by cAMP\u2010dependent protein kinase (PKA) and the stress\u2010activated protein kinases SAPK4\/p38\u03b4 or JNK2 generated the AT100 epitope and that this required phosphorylation of T212, S214 and T217. Tau protein from newborn, but not adult, mouse brain was weakly labelled by AT100. Phosphorylation by PKA and SAPK4\/p38\u03b4 abolished the ability of tau to promote microtubule assembly, but failed to influence significantly the heparin\u2010induced assembly of tau into filaments.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.04052.x","type":"journal-article","created":{"date-parts":[[2006,7,24]],"date-time":"2006-07-24T22:16:26Z","timestamp":1153779386000},"page":"154-164","source":"Crossref","is-referenced-by-count":80,"title":["Sequential phosphorylation of tau protein by cAMP\u2010dependent protein kinase and SAPK4\/p38\u03b4 or JNK2 in the presence of heparin generates the AT100 epitope"],"prefix":"10.1111","volume":"99","author":[{"given":"Hirotaka","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Goedert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1242\/jcs.113.21.3737","article-title":"C\u2010terminal inhibition of tau assembly in vitro and in Alzheimer's disease","volume":"113","author":"Abraha A.","year":"2000","journal-title":"J. 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