ATTACHMENT OF MYRISTIC ACID TO P60SRC

P60src是导致Rous肉瘤病毒致癌的蛋白质， 是一种酪氨酸特异的蛋白激酶。P60src的激酶活性为 这是细胞转化必不可少的，但不是唯一的要求。一个 杨梅酸基团共价连接在氨基末端甘氨酸上 P60src的残留物。P60src的突变体，在该突变体中，该氨基端甘氨酸 被丙氨酸取代，而不是肉豆蔻化。蛋白水解酶活性的变化 这个突变体没有改变，但突变体p60src蛋白不结合到 细胞膜，并且不会改变细胞。肉豆蔻酸 因此，它本身或它所诱导的与膜的结合是必需的 P60src的细胞转化。我们将研究 肉豆蔻酸对p60src的作用有4种方式： 1)通过直接测量肉豆蔻酸化和 P60src氨基末端的非肉豆蔻化多肽类似物； 2)通过开发一种体外肉豆蔻酸化的方法，使脂质和 可以研究肉豆蔻醇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发生肉豆蔻化，以及在哪里 肉豆蔻醇转移酶位于细胞内； 4)在病毒RNA体外翻译过程中，通过使p60src肉豆蔻化 确定蛋白质合成是否是肉豆蔻化所必需的。

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.