Trafficking of Lyn through the Golgi caveolin involves the charged residues on alphaE and alphaI helices in the kinase domain.
Trafficking of Lyn through the Golgi caveolin involves the charged residues on alphaE and alphaI helices in the kinase domain.
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DOI：
10.1083/jcb.200403011
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发表时间：
2004-06-07
影响因子：
7.8
通讯作者：
Yamaguchi, Naoto
中科院分区：
文献类型：
--
作者：
Kasahara, Kousuke;Nakayama, Yuji;Ikeda, Kikuko;Fukushima, Yuka;Matsuda, Daisuke;Horimoto, Shinya;Yamaguchi, Naoto
Src 家族激酶已知参与多种表面受体的信号传导途径，通过脂质修饰定位于质膜的细胞质侧。我们在此表明，Lyn 是 Src 家族激酶的成员，它通过小窝蛋白的高尔基池沿着分泌途径生物合成转运至质膜。 Lyn 从高尔基体到质膜的运输受到激酶结构域缺失或 Csk 诱导的“闭合构象”的抑制，但激酶失活则不受抑制。激酶结构域 C 叶中存在的四个残基（αE 螺旋上的 Asp346 和 Glu353，以及 αI 螺旋上的 Asp498 和 Asp499）可通过“开放构象”暴露于分子表面，被鉴定为参与 Lyn 从高尔基体向质膜的输出，但不靶向高尔基体。因此，Lyn 的激酶结构域除了催化底物磷酸化外，还在 Lyn 运输中发挥作用。
Src-family kinases, known to participate in signaling pathways of a variety of surface receptors, are localized to the cytoplasmic side of the plasma membrane through lipid modification. We show here that Lyn, a member of the Src-family kinases, is biosynthetically transported to the plasma membrane via the Golgi pool of caveolin along the secretory pathway. The trafficking of Lyn from the Golgi apparatus to the plasma membrane is inhibited by deletion of the kinase domain or Csk-induced “closed conformation” but not by kinase inactivation. Four residues (Asp346 and Glu353 on αE helix, and Asp498 and Asp499 on αI helix) present in the C-lobe of the kinase domain, which can be exposed to the molecular surface through an “open conformation,” are identified as being involved in export of Lyn from the Golgi apparatus toward the plasma membrane but not targeting to the Golgi apparatus. Thus, the kinase domain of Lyn plays a role in Lyn trafficking besides catalysis of substrate phosphorylation.