TY - JOUR
T1 - Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases
AU - Goedert, Michel
AU - Hasegawa, Masato
AU - Jakes, Ross
AU - Lawler, Sean
AU - Cuenda, Ana
AU - Cohen, Philip
PY - 1997/6/2
Y1 - 1997/6/2
N2 - The paired helical filament, which comprises the major fibrous element of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated microtubule-associated protein tau. Many of the hyperphosphorylated sites in tau are serine/threonine-prolines. Here we show that the stress-activated protein (SAP) kinases SAPK1γ (also called JNK1), SAPK2a (also called p38, RK, CSBPs, Mpk2 and Mxi2), SAPK2b (also called p38β), SAPK3 (also called ERK6 and p38γ) and SAPK4 phosphorylate tau at many serine/threonine-prolines, as assessed by the generation of the epitopes of phosphorylation-dependent anti-tau antibodies. Based an initial rates of phosphorylation, tau was found to be a good substrate for SAPK4 and SAPK3, a reasonable substrate for SAPK2b and a relatively poor substrate for SAPK2a and SAPK1γ. Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly. These findings double the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders.
AB - The paired helical filament, which comprises the major fibrous element of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated microtubule-associated protein tau. Many of the hyperphosphorylated sites in tau are serine/threonine-prolines. Here we show that the stress-activated protein (SAP) kinases SAPK1γ (also called JNK1), SAPK2a (also called p38, RK, CSBPs, Mpk2 and Mxi2), SAPK2b (also called p38β), SAPK3 (also called ERK6 and p38γ) and SAPK4 phosphorylate tau at many serine/threonine-prolines, as assessed by the generation of the epitopes of phosphorylation-dependent anti-tau antibodies. Based an initial rates of phosphorylation, tau was found to be a good substrate for SAPK4 and SAPK3, a reasonable substrate for SAPK2b and a relatively poor substrate for SAPK2a and SAPK1γ. Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly. These findings double the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders.
KW - Alzheimer's disease
KW - Microtubule assembly
KW - Stress-activated protein kinase
KW - Tau protein
UR - http://www.scopus.com/inward/record.url?scp=0030963035&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(97)00483-3
DO - 10.1016/S0014-5793(97)00483-3
M3 - Article
C2 - 9199504
AN - SCOPUS:0030963035
VL - 409
SP - 57
EP - 62
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1
ER -