IDENTIFICATION OF PROTEIN COMPLEXES AND PHOSPHORYLATION SITES OF PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 McCollum实验室研究了裂解酵母S.pombe中的一条信号通路，称为分隔启动网络(SIN)，它在有丝分裂结束时起作用，触发胞质分裂的启动。SIN途径的大部分成分已被鉴定，但其确切的分子相互作用和磷酸化在其调控中所起的作用尚未确定。我们一直在使用质谱学来表征SIN组分之间的分子相互作用，并确定调节磷酸化的位置。这些研究主要集中在Sid2-Mob1激酶复合体以及SIN的正(CLP1)和负调节(Dma1)。这一途径的所有组成部分在人类中都是保守的，并在胞质分裂和肿瘤抑制中发挥作用。我们已经开始研究，以确定与人类Sid2同源物相互作用的蛋白质，称为Lats2。这些研究应该会导致对酵母中SIN途径的更全面的了解，我们希望这将有助于表征人类的肿瘤抑制途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The McCollum lab studies a signaling pathway in the fission yeast S. pombe, termed the septation initiation network (SIN), which functions at the end of mitosis to trigger initiation of cytokinesis. Most of the components of the SIN pathway have been identified, however their precise molecular interactions and the role phosphorylation plays in their regulation have not been determined. We have been using mass spectrometry to characterize molecular interactions among SIN components and identify sites of regulatory phosphorylation. These studies have focused on the Sid2-Mob1 kinase complex and a positive (Clp1) and negative regulator (Dma1) of the SIN. All of the components of this pathway are conserved in humans and function in cytokinesis and in tumor suppression. We have initiated studies to identify proteins that interact with the human homolog of Sid2, called Lats2. These studies should lead to a more comprehensive understanding of the SIN pathway in yeast, which we hope will help in the characterization of tumor suppression pathways in humans.