Kefalas P, Brown T R, Brickell P M
Department of Molecular Pathology, University College London Medical School, U.K.
Int J Biochem Cell Biol. 1995 Jun;27(6):551-63. doi: 10.1016/1357-2725(95)00024-J.
The c-src gene family has nine known members (blk, c-fgr, fyn, hck, lck, lyn, c-src, c-yes and yrk), each encoding a cytoplasmic protein-tyrosine kinase (PTK) believed to be involved in signal transduction. The c-src PTKs contain three domains (SH1, SH2 and SH3) that are found in many other signalling proteins. The SH1 domain has PTK activity, whilst the SH2 and SH3 domains are involved in mediating protein-protein interactions by binding to phosphotyrosine-containing and proline-rich motifs, respectively. The expression patterns of the c-src PTKs suggest that they function in a broad range of biological situations, in many cases regulating the behaviour of terminally-differentiated, post-mitotic cell types. Targeted disruption of members of the c-src family in transgenic mice has confirmed important roles for p56lck and p59fym(T) in T-lymphocyte maturation and activation, but has also revealed unexpected roles for p60c-src in bone maintenance and for p59fym(B) in learning and memory. There is increasingly detailed information about the biochemical nature of the signalling pathways in which the c-src PTKs operate and about the other signalling proteins with which they interact. The c-src PTKs can associate with activated receptor PTKs, including the receptors for platelet-derived growth factor and epidermal growth factor, by means of SH2-phosphotyrosine binding. The c-src PTKs also associated with transmembrane proteins that lack PTK activity, frequently by means of interactions involving their unique amino-terminal sequences.
c-src基因家族有九个已知成员（blk、c-fgr、fyn、hck、lck、lyn、c-src、c-yes和yrk），每个成员都编码一种细胞质蛋白酪氨酸激酶（PTK），据信该激酶参与信号转导。c-src PTK包含三个结构域（SH1、SH2和SH3），在许多其他信号蛋白中也能找到。SH1结构域具有PTK活性，而SH2和SH3结构域分别通过与含磷酸酪氨酸基序和富含脯氨酸基序结合来介导蛋白质-蛋白质相互作用。c-src PTK的表达模式表明它们在广泛的生物学情况下发挥作用，在许多情况下调节终末分化的有丝分裂后细胞类型的行为。在转基因小鼠中对c-src家族成员进行靶向破坏已证实p56lck和p59fym(T)在T淋巴细胞成熟和激活中起重要作用，但也揭示了p60c-src在骨骼维持以及p59fym(B)在学习和记忆中的意外作用。关于c-src PTK所参与的信号通路的生化性质以及与其相互作用的其他信号蛋白的信息越来越详细。c-src PTK可以通过SH2-磷酸酪氨酸结合与活化的受体PTK结合，包括血小板衍生生长因子和表皮生长因子的受体。c-src PTK还经常通过涉及其独特氨基末端序列的相互作用与缺乏PTK活性的跨膜蛋白结合。
