Martin J H, Mohit A A, Miller C A
Department of Pathology and Neurology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Brain Res Mol Brain Res. 1996 Jan;35(1-2):47-57. doi: 10.1016/0169-328x(95)00181-q.
Mitogen-activated protein (MAP) kinases are proline-directed, serine/threonine kinases that respond to a variety of extracellular signals. A subgroup of these kinases, stress-activated protein (SAP) kinases, phosphorylate c-jun in response to cellular stress. Using monoclonal antibody (MAb) 3F12, we have cloned and partially characterized p493F12 kinase, a mouse homologue of the rat SAP beta kinase and described its expression in the adult and developing mouse. Unlike previously reported MAP and SAP kinases, it is primarily expressed as a 2.7 kb transcript in neurons in the nervous system of the adult mouse. A 2.4 kb transcript is also expressed in the testis. Immunocytochemically, MAb 3F12 decorates a loop-like structure encircling the nucleus in the cytoplasm of neurons in the adult brain, and distinct perinuclear dots in the embryos. In situ hybridization first reveals expression in post-mitotic neurons, on embryonic day 11. The mRNA is also expressed in the Neuro-2A neuroblastoma cell line and is not upregulated in response to differentiating agents. The neuronal specificity of this kinase suggests the presence of a signal transduction cascade unique to neurons. As the amino acid sequence is highly conserved in the human and mouse, the latter may serve as a model for regulation and expression of this kinase.
丝裂原活化蛋白(MAP)激酶是脯氨酸定向的丝氨酸/苏氨酸激酶,可对多种细胞外信号作出反应。这些激酶的一个亚组,即应激激活蛋白(SAP)激酶,可在细胞应激时使c-jun磷酸化。利用单克隆抗体(MAb)3F12,我们克隆并部分鉴定了p493F12激酶,它是大鼠SAPβ激酶的小鼠同源物,并描述了其在成年和发育中小鼠体内的表达情况。与先前报道的MAP和SAP激酶不同,它在成年小鼠神经系统的神经元中主要以2.7 kb的转录本形式表达。在睾丸中也表达一种2.4 kb的转录本。免疫细胞化学分析显示,MAb 3F12在成年大脑神经元细胞质中环绕细胞核的环状结构以及胚胎中的核周明显小点上有标记。原位杂交首先显示在胚胎第11天有丝分裂后的神经元中表达。该mRNA也在Neuro-2A神经母细胞瘤细胞系中表达,并且在分化剂作用下不会上调。这种激酶的神经元特异性表明存在一种神经元特有的信号转导级联反应。由于该氨基酸序列在人和小鼠中高度保守,后者可作为研究这种激酶调节和表达的模型。