Giasson B I, Mushynski W E
Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada.
J Biol Chem. 1996 Nov 29;271(48):30404-9. doi: 10.1074/jbc.271.48.30404.
The aberrant phosphorylation of the neurofilament high molecular weight subunit (NFH) in the neuronal perikaryon is a common feature of several neurological diseases. We demonstrated a strong correlation between hyperphosphorylation of the NFH carboxyl-terminal domain and activation of stress-activated protein kinase (SAPK) -gamma in PC12 cells. Agents that activated SAPKgamma in PC12 cells also caused the hyperphosphorylation of perikaryal NFH in cultured dorsal root ganglion neurons. The NFH carboxyl-terminal domain was phosphorylated by SAPKgamma in vitro, and the use of peptide substrates indicated that this event occurred preferentially at KSPXE motifs. We propose that SAPKgamma, perhaps in concert with other SAPKs, is involved in the abnormal phosphorylation of perikaryal NFH. This finding could lead to new insights into the etiology of several neurological diseases.
神经丝高分子量亚基（NFH）在神经元胞体中的异常磷酸化是几种神经疾病的共同特征。我们证明了PC12细胞中NFH羧基末端结构域的过度磷酸化与应激激活蛋白激酶（SAPK）-γ的激活之间存在很强的相关性。在PC12细胞中激活SAPKγ的试剂也会导致培养的背根神经节神经元中胞体NFH的过度磷酸化。NFH羧基末端结构域在体外被SAPKγ磷酸化，肽底物的使用表明该事件优先发生在KSPXE基序处。我们提出，SAPKγ可能与其他SAPK协同作用，参与胞体NFH的异常磷酸化。这一发现可能会为几种神经疾病的病因学带来新的见解。
