Atypical MAP Kinase Signal Transduction

项目摘要： MAP激酶（MAPKs）是许多信号转导的调节组分 影响真核细胞生长、分化和运动的途径。结构上 相关的非典型MAPK，以哺乳动物MAPK 15（也称为Erk 8）为代表， Dictyosteoprotein Erk 2不被常规MAPK激酶激活，而是被一些 机制不明，对细胞靶点和反应知之甚少 由非典型MAPK调控。我们最近对一种网骨藻2- 无效突变体表明Erk 2对于多种信号的趋化运动是必需的。 在与其他人的合作中，我们还确定了Erk 2可以磷酸化， 使加塔转录因子GtaC从细胞核易位到细胞质。的 拟议的研究将调查非典型MAPK调节的机制， 利用遗传学和生物化学的方法。将分析Erk 2突变体， 它们响应趋化刺激而被激活的能力。Erk 2调节 将研究GtaC以确定非典型MAPK对接和磷酸化位点。一 基于GtaC核/胞质Erk 2调控的实时荧光报告基因 穿梭将用于研究在细胞周期中单细胞中的非典型MAPK活性。 趋化性和细胞分化。预计该项目的结果将确定 非典型MAPK调节和功能的特定机制，也提供了深入了解 非典型MAPK信号在调节趋化性的信号通路中的作用 反应和细胞分化。该项目还将开发非典型MAPK 报告基因技术，可以帮助分析非典型MAPK功能在其他 真核生物

Project Summary: MAP kinases (MAPKs) are regulatory components of many signal transduction pathways that impact eukaryotic cell growth, differentiation, and movement. Structurally related atypical MAPKs, represented by mammalian MAPK15 (also known as Erk8) and Dictyostelium Erk2, are not activated by conventional MAPK kinases but rather by some unknown mechanism and little is known about the cellular targets and responses regulated by atypical MAPKs. Our recent creation and analysis of a Dictyostelium erk2- null mutant indicates that Erk2 is essential for chemotactic movement to multiple signals. In collaboration with others, we have also determined that Erk2 can phosphorylate and translocate the GATA transcription factor, GtaC, from the nucleus to the cytoplasm. The proposed research will investigate the mechanisms of atypical MAPK regulation and function using genetic and biochemical approaches. Erk2 mutants will be analyzed for their ability to be activated in response to chemotactic stimulation. Erk2 regulation of GtaC will be investigated to define atypical MAPK docking and phosphorylation sites. A real-time fluorescent reporter based on the Erk2 regulation of GtaC nuclear/cytoplasmic shuttling will be used to investigate atypical MAPK activity in single cells during chemotaxis and cell differentiation. The results of this project are expected to identify specific mechanisms of atypical MAPK regulation and function and also provide insight into the role of atypical MAPK signaling in signaling pathways that regulate chemotactic responses and cellular differentiation. The project will also develop atypical MAPK reporter technology that could benefit the analysis of atypical MAPK function in other eukaryotes.