Sato Izumi, Obata Yuuki, Kasahara Kousuke, Nakayama Yuji, Fukumoto Yasunori, Yamasaki Takahito, Yokoyama Kazunari K, Saito Takashi, Yamaguchi Naoto
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
J Cell Sci. 2009 Apr 1;122(Pt 7):965-75. doi: 10.1242/jcs.034843. Epub 2009 Mar 3.
Src-family tyrosine kinases (SFKs), which participate in a variety of signal transduction events, are known to localize to the cytoplasmic face of the plasma membrane through lipid modification. Recently, we showed that Lyn, an SFK member, is exocytosed to the plasma membrane via the Golgi region along the secretory pathway. We show here that SFK trafficking is specified by the palmitoylation state. Yes is also a monopalmitoylated SFK and is biosynthetically transported from the Golgi pool of caveolin to the plasma membrane. This pathway can be inhibited in the trans-Golgi network (TGN)-to-cell surface delivery by temperature block at 19 degrees C or dominant-negative Rab11 GTPase. A large fraction of Fyn, a dually palmitoylated SFK, is directly targeted to the plasma membrane irrespective of temperature block of TGN exit. Fyn(C6S), which lacks the second palmitoylation site, is able to traffic in the same way as Lyn and Yes. Moreover, construction of Yes(S6C) and chimeric Lyn or Yes with the Fyn N-terminus further substantiates the importance of the dual palmitoylation site for plasma membrane targeting. Taken together with our recent finding that Src, a nonpalmitoylated SFK, is rapidly exchanged between the plasma membrane and late endosomes/lysosomes, these results suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain.
Src家族酪氨酸激酶（SFKs）参与多种信号转导事件，已知其通过脂质修饰定位于质膜的胞质面。最近，我们发现Lyn作为SFK家族成员之一，沿着分泌途径经高尔基体区域被胞吐到质膜上。我们在此表明，SFK的运输由棕榈酰化状态决定。Yes也是一种单棕榈酰化的SFK，通过生物合成从窖蛋白的高尔基体池转运到质膜。在19摄氏度的温度阻滞或显性负性Rab11 GTP酶作用下，这条途径在反式高尔基体网络（TGN）到细胞表面的运输过程中会受到抑制。双棕榈酰化的SFK——Fyn的很大一部分直接靶向质膜，而不受TGN出口温度阻滞的影响。缺乏第二个棕榈酰化位点的Fyn（C6S）能够与Lyn和Yes以相同的方式运输。此外，构建Yes（S6C）以及带有Fyn N端的嵌合Lyn或Yes，进一步证实了双棕榈酰化位点对于靶向质膜的重要性。结合我们最近的发现，即非棕榈酰化的SFK——Src在质膜和晚期内体/溶酶体之间快速交换，这些结果表明SFK的运输由SH4结构域中的棕榈酰化状态决定。
