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Published on: May 19, 2016
Effects of MAP4K inhibition on neurite outgrowth
Di Ja Lasham1, Reza K Arta1, Abdul Fuad Hadi1
1Departments of Psychiatry, School of Medicine, and Graduate School of Medical and Dental Sciences, Niigata University, 757 Asahimachi Dori-Ichibancho, Chuo-Ku, Niigata, 951-8510, Japan.
Abstract:
Protein kinases are responsible for protein phosphorylation and are involved in important intracellular signal transduction pathways in various cells, including neurons; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), related to as candidate regulators of neurite outgrowth and synaptogenesis, by examining the effects of a selective MAP4K inhibitor PF06260933. PF06260933 treatments of the cultured neurons reduced neurite lengths, not the number of synapses, and phosphorylation of GAP43 and JNK, relative to the control. These results suggest that MAP4Ks are physiologically involved in normal neuronal development and that the resultant impaired neurite outgrowth by diminished MAP4Ks' activity, is related to psychiatric disorders.
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