PT  - JOURNAL ARTICLE
AU  - Ji-Wu Wang
AU  - Yuzuru Imai
AU  - Bingwei Lu
TI  - Activation of PAR-1 Kinase and Stimulation of Tau Phosphorylation by Diverse Signals Require the Tumor Suppressor Protein LKB1
AID  - 10.1523/JNEUROSCI.5094-06.2007
DP  - 2007 Jan 17
TA  - The Journal of Neuroscience
PG  - 574--581
VI  - 27
IP  - 3
4099  - http://www.jneurosci.org/content/27/3/574.short
4100  - http://www.jneurosci.org/content/27/3/574.full
SO  - J. Neurosci.2007 Jan 17; 27
AB  - Aberrant phosphorylation of tau is associated with a number of neurodegenerative diseases, including Alzheimer's disease (AD). The molecular mechanisms by which tau phosphorylation is regulated under normal and disease conditions are not well understood. Microtubule affinity regulating kinase (MARK) and PAR-1 have been identified as physiological tau kinases, and aberrant phosphorylation of MARK/PAR-1 target sites in tau has been observed in AD patients and animal models. Here we show that phosphorylation of PAR-1 by the tumor suppressor protein LKB1 is required for PAR-1 activation, which in turn promotes tau phosphorylation in Drosophila. Diverse stress stimuli, such as high osmolarity and overexpression of the human β-amyloid precursor protein, can promote PAR-1 activation and tau phosphorylation in an LKB1-dependent manner. These results reveal a new function for the tumor suppressor protein LKB1 in a signaling cascade through which the phosphorylation and function of tau is regulated by diverse signals under physiological and pathological conditions.