Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba, Japan.
Cancer Lett. 2008 Apr 8;262(1):19-27. doi: 10.1016/j.canlet.2007.11.025. Epub 2008 Jan 2.
Overexpression of the c-src proto-oncogene product with its increased kinase activity is observed in numerous cancer types. Oncogenic transformation is often associated with aberrant lysosome distribution. Here, we show that v-Src and c-Src, nonpalmitoylated Src kinases, largely localize to lysosomes and induce perinuclear accumulation of lysosomes through Rab7 in a manner dependent on the SH2 domain but dispensable for the kinase activity. Unlike v-Src and c-Src, the palmitoylated Src kinases c-Yes, Fyn and Lyn localize minimally to lysosomes and marginally affect lysosome distribution. These results suggest that elevated expression of nonpalmitoylated Src plays a critical role in lysosome distribution.
在许多癌症类型中，观察到 c-src 原癌基因产物的过表达及其激酶活性的增加。致癌转化通常与溶酶体分布异常有关。在这里，我们表明，非棕榈酰化的Src 激酶 v-Src 和 c-Src 主要定位于溶酶体，并通过 Rab7 诱导溶酶体在核周聚集，这种方式依赖于 SH2 结构域，但不依赖于激酶活性。与 v-Src 和 c-Src 不同，棕榈酰化的 Src 激酶 c-Yes、Fyn 和 Lyn 极少定位于溶酶体，对溶酶体分布的影响也很小。这些结果表明，非棕榈酰化 Src 的高表达在溶酶体分布中起着关键作用。
