Gómez-Ramos Alberto, Domínguez Jorge, Zafra Delia, Corominola Helena, Gomis Ramon, Guinovart Joan J, Avila Jesús
Centro de Biología Molecular, CSIC/UAM, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
J Neurosci Res. 2006 Feb 1;83(2):264-73. doi: 10.1002/jnr.20726.
Tungstate treatment increases the phosphorylation of glycogen synthase kinase-3beta (GSK3beta) at serine 9, which triggers its inactivation both in cultured neural cells and in vivo. GSK3 phosphorylation is dependent on the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) induced by tungstate. As a consequence of GSK3 inactivation, the phosphorylation of several GSK3-dependent sites of the microtubule-associated protein tau decreases. Tungstate reduces tau phosphorylation only in primed sequences, namely, those prephosphorylated by other kinases before GSK3beta modification, which are serines 198, 199, or 202 and threonine 231. The phosphorylation at these sites is involved in reduction of the interaction of tau with microtubules that occurs in Alzheimer's disease.
钨酸盐处理会增加糖原合酶激酶-3β（GSK3β）丝氨酸9位点的磷酸化，这会在培养的神经细胞和体内触发其失活。GSK3的磷酸化依赖于钨酸盐诱导的细胞外信号调节激酶1/2（ERK1/2）的激活。由于GSK3失活，微管相关蛋白tau的几个GSK3依赖位点的磷酸化减少。钨酸盐仅在引发序列中降低tau磷酸化，即在GSK3β修饰之前被其他激酶预磷酸化的序列，这些序列是丝氨酸198、199或202以及苏氨酸231。这些位点的磷酸化参与了阿尔茨海默病中tau与微管相互作用的减少。
