MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism.
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.
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, New Jersey, United States of America.
Laura P
LP
Bernard
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, New Jersey, United States of America.
Huaye
H
Zhang
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D047428:Protein Kinase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; C484552:Mark1 protein, rat; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases