THE SMKI MAPK AND SPORE DEVELOPMENT IN SACCHAROMYCES

丝裂原活化蛋白激酶（MAPKs）包括一个进化上保守的信号转导酶家族，该家族在响应各种上游信号时磷酸化调节分子。对环境变化的适应性反应、对有丝分裂原的增殖反应以及对发育过程中发生的信号的分化反应都需要MAPKs。与胚胎发育和细胞增殖控制相关的一个重要问题涉及MAPK通路如何调节发育过程。SMK1编码减数分裂发育所需的MAPK，是发育的良好模式系统。本研究将利用SMK1和孢子形成来阐明调控细胞分化程序的MAPK信号通路的分子机制。一系列条件smk1突变体已经产生，并在遗传、生化和超微结构水平上进行了表征（Wagner et al. 1999, Genetics 151:1327）。在本提案的目标1中，这些突变体将用于：利用敏感的遗传背景识别SMK1信号通路的新成分。为了从这些遗传研究中推断生化机制，有必要发展生化方法来研究Smk1。在目标2的研究中，我们将阐明纺锤体在调节SMK1功能中的作用。在细胞中（Pierce et a. 1998, Mol. Cell）。《圣经》18:59 . 70。EMO J.出版)。在目标4实验描述将：阐明SMK1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.