Cdk5/p35 phosphorylates lemur tyrosine kinase-2 to regulate protein phosphatase-1C phosphorylation and activity.
Cyclin-dependent kinase-5 (cdk5)/p35 and protein phosphatase-1 (PP1) are two major enzymes that control a variety of physiological processes within the nervous system including neuronal differentiation, synaptic plasticity and axonal transport. Defective cdk5/p35 and PP1 function are also implicated in several major human neurodegenerative diseases. Cdk5/p35 and the catalytic subunit of PP1 (PP1C) both bind to the brain-enriched, serine-threonine kinase lemur tyrosine kinase-2 (LMTK2). Moreover, LMTK2 phosphorylates PP1C on threonine-320 (PP1Cthr³²⁰) to inhibit its activity. Here, we demonstrate that LMTK2 is phosphorylated on serine-1418 (LMTK2ser¹⁴¹⁸) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate PP1Cthr³²⁰. We thus describe a new signalling pathway within the nervous system that links cdk5/p35 with PP1C and which has implications for a number of neuronal functions and neuronal dysfunction.
Departments of Neuroscience and Clinical Neurosciences, Institute of Psychiatry, King's College London, London, UK.
Catherine
C
Manser
Alessio
A
Vagnoni
Florence
F
Guillot
Jennifer
J
Davies
Christopher C J
CC
Miller
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007900:Lemur / Q000502:physiology*; D013058:Mass Spectrometry; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D053634:TYK2 Kinase / Q000378:metabolism*; D014162:Transfection
D053634:TYK2 Kinase; D051360:Cyclin-Dependent Kinase 5; D054645:Protein Phosphatase 1