GENETIC ANALYSIS OF NEURAL SAPK SCAFFOLD

描述（逐字摘自申请人的摘要）：图谱激酶级联 真核细胞中的功能是将细胞外信号传递和翻译成 细胞生物学反应。 MAPK 包括应激激活蛋白激酶 (SAPK) 可以调节细胞形状、细胞凋亡和神经肌肉 协调。 FIP 是一种新分离的 SAPK 支架蛋白，表达于 具有与成纤维细胞生长结合的不寻常特性的神经元 因子同源蛋白（FHF）。与 FHF-2 结合使用，FIP 可以 协调上游激酶对 SAPK4/p38delta 的特异性激活 MLK-3。因此，虽然 FHF 在结构上与成纤维细胞生长因子相关， 假设 FHF 作为 SAPK 激酶的一部分在细胞内发挥作用 神经元细胞中的信号传导模块。 提出了一系列小鼠遗传实验来研究 FIP 的神经生物学功能及其对 FHF 介导的依赖性 SAPK4/p38delta 激活。这些实验包括（I）生成和 FIP缺陷小鼠的分析，（II）鉴定不能的FIP突变体 结合FHF，以及（III）携带这种突变的小鼠的产生和分析 在 FIP 中。除了定义与相关的表型的重要性之外 破坏新的生化途径，这些研究可能会显着 提高我们对神经元发育机制的理解 功能。

DESCRIPTION (Verbatim from the Applicant's Abstract): Map kinase cascades function in eukaryotic cells to relay and translate extracellular signals into cellular biological responses. MAPKs include stress activated protein kinases (SAPKs) which can regulate cell shape, apoptosis, and neuromuscular coordination. FIP is a newly-isolated SAPK scaffold protein expressed in neuronal which has the unusual property of binding to fibroblast growth factor-homologous proteins (FHFs). In conjunction with FHF-2, FIP can coordinate the specific activation of SAPK4/p38delta by the upstream kinase MLK-3. Hence, while FHFs are structurally related to fibroblast growth factors, FHFs are hypothesized to function intracellularly as part of a SAPK kinase signalling module in neuronal cells. A series of mouse genetic experiments are proposed to investigate both the neurobiological function of FIP and its dependence upon FHFs to mediate SAPK4/p38delta activation. These experiments include (I) generation and analysis of FIP-deficient mice, (II) identification of FIP mutants incapable of binding FHF, and (III) generation and analysis of mice carrying such a mutation in FIP. In addition to the importance of defining the phenotype associated with disruption of a new biochemical pathway, these studies may significantly improve our understanding of mechanisms underlying neuronal development and function.