GENETIC ANALYSIS OF REGULATION AND FUNCTION OF CD45

白细胞共同抗原CD45已受到相当大的关注 最近，随着越来越多的证据表明它在信号转导中的作用， 在免疫反应中。 CD45具有以下有趣的性质：（a） 表达限于有核造血细胞，（B）多个 在细胞外结构域中不同的同种型，（c）严格 不同亚型在不同细胞中的调节表达 造血谱系，（d）具有蛋白质的大胞质结构域 酪氨酸磷酸酶（PTK）活性和（e）与 在细胞表面参与信号转导的复合物。 的CD45 分子似乎是一个重要的参与者的功能， 对细胞系的研究表明，CD45是 通过T和B上的细胞表面受体对最佳信号传导至关重要 淋巴细胞和可能的，通过外推，其他造血谱系 细胞 胞质结构域的PTB活性似乎是关键的， 信号功能。正在出现的模型是CD45功能 为了控制src家族蛋白酪氨酸的磷酸化状态 激酶，其成员已被证明在信号传导中发挥作用 通过T细胞受体和B细胞抗原受体。 校长 迄今为止的研究导致了我们目前对CD 45功能的概念 使用人工体外系统。 阻碍进展的主要问题 在回答关于CD45及其作用的进一步问题时， 从其cDNA表达CD45的能力。 即使成功，其他 不具有CD45的独特表达特征的启动子 必须被使用。 所提出的实验解决了以下功能： CD45结构成分在体内通过引入突变到 完整的CD45基因 细胞外结构域， 胞质结构域和关键功能位点将在 这种方式。

The leukocyte common antigen CD45 has received considerable attention recently as evidence accumulates for its role in signal transduction during immune responses. CD45 has the interesting properties of (a) expression restricted to nucleated hematopoietic cells, (b) multiple isoforms which differ in the extracellular domain, (c) strictly regulated expression of the different isoforms in the various hematopoietic lineages, (d) a large cytoplasmic domain with protein tyrosine phosphatase (PTPase) activity and (e) associations with complexes at the cell surface involved in signal transduction. The CD45 molecule appears to be an important participant in the function of the cells expressing it. Studies with cell lines have indicated CD45 is essential for optimal signaling via cell surface receptors on T and B lymphocytes and possibly, by extrapolation, other hematopoietic lineage cells. The PTPase activity of the cytoplasmic domain appears critical for the signaling function. The model that is emerging is CD45 functions to control the state of phosphorylation of src family protein tyrosine kinases, members of which have been shown to play roles in signaling through the T cell receptor and B cell antigen receptor. The principal studies to date that have led to our present concept of CD45 function have used artificial in vitro systems. A major issue hindering progress in answering further questions concerning CD45 and its role is the poor ability to express CD45 from its cDNA. Even when successful, other promoters not having the distinctive expression characteristics of CD45 have had to be used. The experiments proposed address the function of CD45 structural components in vivo by introducing mutations into the complete CD45 gene. The roles of the extracellular domain, the cytoplasmic domain and critical functional sites will be evaluated in this manner.