MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism

被引：21
作者：
Bernard, Laura P. [1 ]
Zhang, Huaye [1 ]
机构：
[1] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA
来源：
PLOS ONE | 2015年 / 10卷 / 05期
基金：
美国国家卫生研究院;
关键词：
LONG-TERM POTENTIATION; DENDRITIC SPINE MORPHOLOGY; SYNAPTIC PLASTICITY; PROTEIN-KINASE; PHOSPHORYLATION; POLARITY; PSD-95; LKB1; NEURONS; SYNAPTOGENESIS;
D O I：
10.1371/journal.pone.0124816
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs), are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer's disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA), through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1. Together, our data reveal a novel mechanism by which MARK/Par1 is activated at the neuronal synapse.
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页数：11
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