The Src29A Tyrosine Kinase Gene of Drosophila

*9514790个与src相关的贝肯多夫胞质蛋白酪氨酸激酶组成了一个庞大且不断增长的家族，参与了许多信号转导途径。它们都局限于细胞质，大多数与质膜的内面有关。它们通常与跨膜受体的细胞质部分相互作用，其激酶活性受到配体与受体结合的刺激。Src家族的活性受到严格的控制，因此它们在受到刺激之前是不活跃的。这一调控的重要性从Src和该家族其他几个成员的突变中可见一斑，这些突变导致了结构性激酶活性和致癌转化。最近定义的Src相关蛋白亚家族包括三个哺乳动物基因Btk、itk和tec，它们都在哺乳动物的造血细胞中表达，以及果蝇基因Src29A。这些基因缺乏D-末端酪氨酸，而D-末端酪氨酸对大多数Src家族的酶有负面调节作用。它们也缺乏将该家族的其他成员固定在质膜上的N-末端肉豆蔻化位点。取而代之的是，亚家族的成员有一个延伸的N-末端同源区域，暗示着与其他蛋白质的相互作用。由于这些结构上的差异，这个亚家族的成员可能在功能上不同于先前描述的Src家族的激酶，可能参与不同的信号通路或在熟悉的通路中处于不同的水平。虽然Src29A在十多年前就被发现，但人们对其功能知之甚少。然而，它在造血细胞中高度表达，在哺乳动物中也是如此。本项目旨在通过分析Src29A！的合子表型和母体表型来研究其功能。变种人。贝肯多夫博士最近发现了几个可以使Src29A失活的P元件插入物，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，并试图确定哪条信号转导途径需要这种酪氨酸激酶。***

*** 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. ***