THE SMKI MAPK AND SPORE DEVELOPMENT IN SACCHAROMYCES

有丝分裂原活化蛋白激酶（MAPK）包括响应于多种上游信号而磷酸化调节分子的进化上保守的信号转导酶家族。MAPK是对环境变化的适应性反应、对有丝分裂原的增殖反应和对发育过程中发生的信号的分化反应所必需的。与胚胎发育和细胞增殖控制相关的一个重要问题涉及MAPK途径如何调节发育过程。SMK1编码减数分裂发育所需的MAPK，是发育的极好模型系统。本研究将使用SMK1和孢子形成来阐明MAPK信号通路中调节细胞分化程序的分子机制。已经在遗传、生物化学和超微结构水平上产生并表征了条件性smk 1突变体的集合（瓦格纳等人，1999，遗传学151：1327）。在本提案的目标1中，这些突变体将用于：使用致敏遗传背景鉴定SMK1信号通路的新组分。为了从这些遗传学研究的生化机制的基础上的推论，有必要发展的生化方法来研究Smk 1。在目标2研究中，我们将：阐明纺锤体极体在调节SMK 1功能中的作用。在细胞中（Pierce et a. 1998，Mol. Cell. 18：5970，即等EMO J.出版中）。在目标4的实验中，将：阐明SMK 1转录调控途径在控制减数分裂发育进程中的作用。

Mitogen activated protein kinases (MAPKs) comprise an evolutionarily conserved family of signal transducing enzymes that phosphorylate regulatory molecules in response to a broad variety of upstream signals. MAPKs are required for adaptive responses to changes in the environment, proliferative responses to mitogens, and differentiative responses to signals that occur during development. An important issue that is relevant to embryological development and the control of cell proliferation concerns how MAPK pathways regulate developmental processes. SMK1, encodes a MAPK that is required for meiotic development an excellent model system for development. This study will use SMK1 and sporulation to elucidate molecular mechanisms in MAPK signaling pathways that regulate cellular differentiation programs. A collection of conditional smk1 mutants has already been generated and characterized at the genetic, biochemical and ultrastructural levels (Wagner et al. 1999, Genetics 151:1327). In aim 1 of this proposal these mutants will be used to: Identify new components of the SMK1 signaling pathways using sensitized genetic backgrounds. In order to ground the inferences from these genetic studies in biochemical mechanism it is necessary to develop biochemical approaches to study Smk1. In aim 2 studies we will: Elucidate the role of the spindle pole body in regulating SMK1 function. In cells (Pierce et a. 1998, Mol. Cell. Biol. 18:5970, i.e. et al. EMO J. in press). In aim 4 experiments are described that will: Elucidate the role of the SMK1 transcriptional regulatory pathway in controlling progression of meiotic development.