P70 S6 kinase mediates tau phosphorylation and synthesis.
Currently, we found that the 70-kDa p70 S6 kinase (p70S6K) directly phosphorylates tau at S262, S214, and T212 sites in vitro. By immunoprecipitation, p-p70S6K (T421/S424) showed a close association with p-tau (S262 and S396/404). Zinc-induced p70S6K activation could only upregulate translation of total S6 and tau but not global proteins in SH-SY5Y cells. The requirement of p70S6K activation was confirmed in the SH-SY5Y cells that overexpress wild-type htau40. Level of p-p70S6K (T421/S424) was only significantly correlated with p-tau at S262, S214, and T212, but not T212/S214, in Alzheimer's disease (AD) brains. These suggested that p70S6K might contribute to tau related pathologies in AD brains.
Pei
Jin-Jing
JJ
Department of Neurotec, Division of Experimental Geriatrics, Karolinska Institutet, KFC Novum, Plan 4, SE-141 86, Huddinge, Sweden. Jin-Jing.Pei@neurotec.ki.se
An
Wen-Lin
WL
Zhou
Xin-Wen
XW
Nishimura
Takeshi
T
Norberg
Jan
J
Benedikz
Eirikur
E
Götz
Jürgen
J
Winblad
Bengt
B
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology; D016875:tau Proteins
D008565:Membrane Proteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D012694:Serine; D013912:Threonine; D015032:Zinc; C054369:MAPT protein, human; D016875:tau Proteins