Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen
Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen
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DOI：
10.1074/jbc.m201078200
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发表时间：
2002-05-24
影响因子：
4.8
通讯作者：
Lin, HC
中科院分区：
文献类型：
--
作者：
Ikeda, K;Wang, LH;Lin, HC
盘状结构域受体 2 (DDR2) 是一种不寻常的受体酪氨酸激酶，因为它的配体是纤维状胶原而不是生长因子样肽。我们检查了 DDR2 的信号转导途径。在这里，我们表明 DDR2 的不寻常之处在于它需要 Src 活性最大限度地酪氨酸磷酸化，并且 Src 活性还促进 DDR2 与 Shc 的关联。与 Shc 的相互作用涉及 She 的一部分，之前未涉及与受体酪氨酸激酶的相互作用。这些结果将 Src 激酶和接头蛋白 Shc 确定为 DDR2 信号转导中的关键信号中间体。此外，Src 是 DDR2 介导的基质金属蛋白酶-2 启动子反式激活所必需的。这些数据支持一个模型，其中 Src 和 DDR2 受体以受调控的方式合作，指导受体及其靶标的磷酸化。
Discoidin domain receptor 2 (DDR2) is an unusual receptor tyrosine kinase in that its ligand is fibrillar collagen rather than a growth factor-like peptide. We examined signal transduction pathways of DDR2. Here we show that DDR2 is also unusual in that it requires Src activity to be maximally tyrosine-phosphorylated, and that Src activity also promotes association of DDR2 with Shc. The interaction with Shc involves a portion of She not previously implicated in interaction with receptor tyrosine kinases. These results identify Src kinase and the adaptor protein Shc as key signaling intermediates in DDR2 signal transduction. Furthermore, Src is required for DDR2-mediated transactivation of the matrix metalloproteinase-2 promoter. The data support a model in which Src and the DDR2 receptor cooperate in a regulated fashion to direct the phosphorylation of both the receptor and its targets.