Differential trafficking of Src, Lyn, Yes and Fyn is specified by the state of palmitoylation in the SH4 domain
Differential trafficking of Src, Lyn, Yes and Fyn is specified by the state of palmitoylation in the SH4 domain
复制标题
DOI：
10.1242/jcs.034843
复制
发表时间：
2009-04-01
影响因子：
4
通讯作者：
Yamaguchi, Naoto
中科院分区：
文献类型：
--
作者：
Sato, Izumi;Obata, Yuuki;Yamaguchi, Naoto
SRC家族酪氨酸激酶(SFK)参与多种信号转导过程，通过脂质修饰定位于细胞膜表面。最近，我们发现作为SFK成员的Lyn沿着分泌途径通过高尔基体区域被胞吐到质膜。我们在这里表明，SFK的贩运是由棕榈酰化状态指定的。YES也是一种单丝裂化的SFK，以生物合成的方式从高尔基囊泡转运到质膜上。在跨高尔基体网络(TGN)到细胞的表面传递中，这一途径可以被19℃的温度阻断或显性负的Rab11 GTP酶抑制。Fyn是一种双棕榈酰化的SFK，它的很大一部分直接作用于质膜，而与TGN出口的温度无关。Fyn(C6s)缺乏第二个棕榈酰化位点，能够以与Lyn和Yes相同的方式进行运输。此外，YES(S6C)和嵌合LYN或YES与FYN-末端的构建进一步证实了双棕榈酰化位点对于质膜靶向的重要性。结合我们最近的发现，一种非棕榈酰化的SFK，在质膜和晚期内小体/溶酶体之间快速交换，这些结果表明SFK的运输是由SH4结构域中的棕榈酰化状态决定的。
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.