Journal of Cell Science, Vol 113, Issue 3 401-407, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3

J Brownlees, A Yates, NP Bajaj, D Davis, BH Anderton, PN Leigh, CE Shaw and CC Miller
Department of Neuroscience, The Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.

Neurofilaments comprise three subunit proteins; neurofilament light, middle and heavy chains (NF-L, NF-M and NF-H). The carboxy-terminal domains of NF-M and NF-H form side-arms that project from the filament and that of NF-H contains multiple repeats of the motif lys-ser-pro, the serines of which are targets for phosphorylation. The level of phosphorylation on the lys-ser-pro repeats varies topographically within the cell; in cell bodies and proximal axons, the side-arms are largely non-phosphorylated whereas in more distal regions of axons, the side-arms are heavily phosphorylated. Here we show that stress activated protein kinase 1b (SAPK1b), a major SAPK in neurones will phosphorylate NF-H side-arms both in vitro and in transfected cells. These studies suggest that SAPK1b targets multiple phosphorylation sites within NF-H side-arms. Additionally, we show that glutamate treatment induces activation of SAPK1b in primary cortical neurones and increased phosphorylation of NF-H in cell bodies. This suggests that glutamate causes increased NF-H phosphorylation at least in part by activation of stress activated protein kinases.

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