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

TY - JOUR

T1 - Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3

AU - Brownlees, J

AU - Yates, A

AU - Bajaj, N P

AU - Davis, D

AU - Anderton, B H

AU - Leigh, P N

AU - Shaw, C E

AU - Miller, C C J

PY - 2000

Y1 - 2000

N2 - 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 nonphosphorylated 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.

AB - 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 nonphosphorylated 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.

UR - http://www.scopus.com/inward/record.url?scp=0033994852&partnerID=8YFLogxK

M3 - Article

VL - 113

SP - 401

EP - 407

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 3

ER -