ATTACHMENT OF MYRISTIC ACID TO P60SRC

p60 src，负责劳斯肉瘤病毒致癌性的蛋白， 是酪氨酸特异性蛋白激酶。 p60 src的激酶活性是 这是细胞转化的必要条件，但不是唯一的要求。 一 肉豆蔻酸基团共价连接到氨基末端甘氨酸 p60 src的残基。 p60 src的突变体，其中该氨基末端甘氨酸 被丙氨酸取代的未被肉豆蔻酰化。 的激酶活性 该突变体是未改变的，但是突变的p60 src蛋白不结合至 细胞膜，并且不转化细胞。 肉豆蔻酸 它本身，或它诱导的与膜的结合，因此是必需的， 通过p60 src的细胞转化。 我们将研究 肉豆蔻酸对p60 src有4种作用： 1)通过直接测量肉豆蔻酰化和 p60 src的氨基末端的非肉豆蔻基化肽类似物; 2)通过开发肉豆蔻酰化的体外方法， 可以研究肉豆蔻基转移酶的底物特异性; 3)通过确定新生多肽链是否含有肉豆蔻酸， 了解蛋白质在合成过程中是否会被肉豆蔻基化， 肉豆蔻基转移酶位于细胞内; 4)通过在病毒RNA的体外翻译过程中使p60 src多肉豆蔻酰化， 确定蛋白质合成是否是肉豆蔻酰化的必要条件。

p60src, the protein responsible for the oncogenicity of Rous sarcoma virus, is a tyrosine-specific protein kinase. The kinase activity of p60src is essential but is not the only requirement for cellular transformation. A myricstic acid group is covalently attached to the amino terminal glycine residue of p60src. A mutant of p60src in which this amino terminal glycine is replaced with an alanine is not myristylated. The kinase activity of this mutant is unaltered, but the mutant p60src protein does not bind to cellular membranes, and does not transform cells. The myristic acid itself, or the binding to membranes which it induces is thus required for cellular transformation by p60src. We will study the function of the myristic acid for p60src in 4 ways: 1) by measuring directly the membrane-binding of myristylated and non-myristylated peptide analogs of the amino terminus of p60src; 2) by developing an in vitro method of myristylation so that the lipid and substrate specificities of the myristyl transferase may be studied; 3) by determining if nascent polypeptide chains contain myristic acid to learn if proteins become myristylated during synthesis and where the myristyl transferase in located in the cell; 4) by myristylating p60src during in vitro translation of viral RNA to determine if protein synthesis is a requirement for myristylation.