Silverman L, Resh M D
Department of Cell Biology and Genetics, Memorial Sloan-Kettering Cancer, Center, New York 10021.
J Cell Biol. 1992 Oct;119(2):415-25. doi: 10.1083/jcb.119.2.415.
Association of pp60v-src with the plasma membrane is fundamental to generation of the transformed phenotype. Although myristylation of pp60v-src is required for interaction with a membrane-bound receptor, the importance of NH2-terminal amino acids in receptor binding has not yet been uncoupled from their role in signaling myristylation. Using chimeric src proteins, peptides identical or related to the NH2 terminus of src, and site-directed mutagenesis, we demonstrate that NH2-terminal lysines in conjunction with myristate are essential for membrane localization. Subsequent to NH2-terminal interaction with the "src receptor," internal regions of the src protein also participate in membrane binding. This novel NH2-terminal motif and internal contact mechanism may direct other members of the src family of tyrosine kinases to their membrane receptors.
pp60v-src与质膜的结合对于转化表型的产生至关重要。虽然pp60v-src的肉豆蔻酰化是与膜结合受体相互作用所必需的，但src氨基末端氨基酸在受体结合中的重要性尚未与其在肉豆蔻酰化信号传导中的作用区分开来。通过使用嵌合src蛋白、与src氨基末端相同或相关的肽以及定点诱变，我们证明氨基末端赖氨酸与肉豆蔻酸结合对于膜定位至关重要。在氨基末端与“src受体”相互作用之后，src蛋白的内部区域也参与膜结合。这种新的氨基末端基序和内部接触机制可能会将酪氨酸激酶src家族的其他成员导向其膜受体。
