The Src29A Tyrosine Kinase Gene of Drosophila

果蝇Src29A酪氨酸激酶基因

• 批准号: 9514790
• 负责人: Steven Beckendorf
• 金额: $ 11万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9514790&HistoricalAwards=false
• 关键词: Src29A; Tyrosine; Kinase; Gene; Drosophila

*** 9514790 Beckendorf Cytoplasmic protein tyrosine kinases related to Src constitute a large and growing family involved in many signal transduction pathways. All are confined to the cytoplasm and most are associated with the inner face of the plasma membrane. They typically interact with the cytoplasmic portion of transmembrane receptors, and their kinases activity is stimulated by binding of ligands to the receptors. The activity of Src-family kinases is under tight control so that they are inactive until stimulated. The importance of this regulation is shown by the mutations in Src and several other members of this family that result in constitutive kinase activity and oncogenic transformations. A recently defined subfamily of Src-related kinases includes three mammalian genes, btk, itk and tec, that are all expressed in mammalian hematopoietic cells, and the Drosophila gene Src29A. These genes are lacking the D-terminal tyrosine that negatively regulates most Src-family kinases. They also lack an N-terminal myristylation site that anchors other members of the family to the plasma membrane. In its place members of the subfamily have an extended region of N-terminal homology that implies interactions with other proteins. Because of these structural differences members of this subfamily are likely to be functionally distinct from the previously characterized Src-family kinases, perhaps participating in different signaling pathways or at different levels in familiar pathways. Although Src29A was identified over ten years ago, little is known about its function. It is, however, highly expressed in hematopoietic cells as are its mammalian counterparts. This project seeks to study Src29A function by analyzing zygotic and maternal phenotypes of Src29A! mutants. Dr. Beckendorf has recently identified several P element inserts that inactivate Src29A and have shown that the gene is required for head development. Now he will examine the maternal effects of these mutations and attempt to determin e which signal transduction pathway requires this tyrosine kinase. ***

* 9514790贝肯多夫 与Src相关的胞质蛋白酪氨酸激酶组成了一个庞大且不断增长的家族，参与许多信号转导途径。所有这些都局限于细胞质中，大多数与质膜的内表面有关。它们通常与跨膜受体的细胞质部分相互作用，并且它们的激酶活性通过配体与受体的结合而被刺激。Src家族激酶的活性受到严格控制，因此它们在受到刺激之前是无活性的。这种调节的重要性表现在Src和该家族的其他几个成员的突变，导致组成性激酶活性和致癌转化。最近定义的Src相关激酶亚家族包括三个哺乳动物基因，btk，itk和tec，它们都在哺乳动物造血细胞中表达，以及果蝇基因Src 29 A。这些基因缺乏负调节大多数Src家族激酶的D-末端酪氨酸。它们也缺乏将家族其他成员锚定到质膜的N-末端肉豆蔻基化位点。在其位置上，该亚家族的成员具有延伸的N-末端同源性区域，这意味着与其他蛋白质的相互作用。由于这些结构上的差异，该亚家族的成员可能在功能上不同于先前表征的Src家族激酶，可能参与不同的信号传导途径或在不同水平上参与熟悉的途径。虽然Src 29 A在十多年前就被发现了，但对其功能知之甚少。然而，它在造血细胞中高度表达，其哺乳动物对应物也是如此。本项目旨在通过分析Src 29 A的合子和母体表型来研究Src 29 A的功能！变种人Beckendorf博士最近发现了几个插入Src 29 A的P元件，并表明该基因是头部发育所必需的。现在，他将研究这些突变对母体的影响，并试图确定哪种信号转导途径需要这种酪氨酸激酶。 ***