REGULATION OF P55/HDLG INTERACTION WITH PROTEIN 4.1

p55是一种棕榈酰化的外周膜磷蛋白， 血细胞p55与蛋白4.1和血型糖蛋白C形成复合物。 这种蛋白质复合物在遗传异常的红细胞中缺失 改变了形状并显著降低了膜的稳定性。虽然 p55的确切生理作用是未知的，对该组分的兴趣 由于它与果蝇的圆盘状大肿瘤相似， 抑制蛋白p55和最近克隆的Hdlg（人B淋巴细胞 大果蝇（Drosophila discs-large）的同源物）是一个不断增长的家族的成员 这种蛋白质被认为在信号传导过程中起作用， 在膜-细胞骨架界面的转导。本课题 希望研究人p55和Hdlg与细胞骨架的相互作用， 蛋白4.1，并确定这些相互作用是否受 鸟嘌呤核苷酸和磷酸化。这些长期目标 研究的目的是检验MAGUKs和 蛋白质4.1同源物是广泛存在的并且在生理学上是重要的。 使用本项目开发的蛋白结合试验，我们将确定 如果其它MAGUKs如果蝇Dlg、紧密连接Z 0 -1和C. elegans LIN-2蛋白也与蛋白4.1结合。与博士合作。 安德森，我们将测试p55和Hdlg的酪氨酸磷酸化是否 发生在哺乳动物细胞系统的条件下， 实验室总之，MAGUKs和蛋白4.1之间的相互作用 可能作为信号转导的重要位点出现， 膜-细胞骨架连接。

p55 is a palmitoylated peripheral membrane phosphoprotein of human red blood cells. p55 forms a complex with protein 4.1 and glycophorin C. This protein complex is missing in genetically abnormal red blood cells with altered shape and markedly reduced membrane stability. Although the precise physiological role of p55 is unknown, interest in this component has been heightened by its similarity to the Drosophila discs-large tumor suppressor protein. p55 and recently cloned Hdlg (human B lymphocyte homologue of the Drosophila discs-large) are members of a growing family of proteins called MAGUKs which are believed to play a role during signal transduction at the membrane-cytoskeleton interface. In this project, we wish to study the interaction of human p55 and Hdlg with cytoskeletal protein 4.1, and determine whether these interactions are regulated by guanine nucleotides and phosphorylation. The long-term goal of these studies is to test the hypothesis that interaction between MAGUKs and protein 4.1 homologues are widespread and physiologically important. Using protein binding assays developed in this project, we will determine if other MAGUKs such as Drosophila Dlg, tight junction Z0-1 and C. elegans LIN-2 proteins also bind to protein 4.1. In collaboration with Dr. Anderson, we will test whether tyrosine phosphorylation of p55 and Hdlg occurs in mammalian cell systems under the conditions developed in his laboratory. In summary, the interactions between MAGUKs and protein 4.1 may emerge as a generally important site for signal transduction and membrane-cytoskeleton linkage.