Metalloprotease-disintegrin ADAM 12 binds to the SH3 domain of Src and activates Src tyrosine kinase in C2C12 cells.
Metalloprotease-disintegrin ADAM 12 binds to the SH3 domain of Src and activates Src tyrosine kinase in C2C12 cells.
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DOI：
10.1042/bj3520883
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发表时间：
2000-12
期刊：
影响因子：
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通讯作者：
Qing Kang;Yi-Chun Cao;A. Zolkiewska
中科院分区：
文献类型：
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作者：
Qing Kang;Yi-Chun Cao;A. Zolkiewska
ADAM 12 是金属蛋白酶解整合素 ADAM（含有解整合素和金属蛋白酶的蛋白质）家族的成员，与骨骼肌成肌细胞的分化和融合有关，并且其表达在许多癌细胞中显着上调。虽然 ADAM 12 的胞外部分包含活性金属蛋白酶和细胞粘附结构域，但胞质部分的功能尚不清楚。在本文中，我们证明 ADAM 12 的胞质尾介导与非受体蛋白酪氨酸激酶 Src 的相互作用。这种相互作用是直接、特异性的，涉及 ADAM 12 细胞质尾部的 N 端富含脯氨酸的区域和 Src 的 Src 同源 3 (SH3) 结构域。 ADAM 12 和 Src 从转染的 C2C12 细胞中进行免疫共沉淀，表明这两种蛋白质在体内形成复合物。在 C2C12 细胞中，Src 和 ADAM 12（但不是 ADAM 9）共表达会导致重组 Src 的激活。此外，内源性 ADAM 12 在分化的 C2C12 细胞中与内源性 Src 结合并激活内源性 Src。这些结果表明 ADAM 12 可能在成肌细胞分化过程中介导粘附诱导的信号传导。
ADAM 12, a member of the ADAM (protein containing a disintegrin and metalloprotease) family of metalloprotease-disintegrins, has been implicated in the differentiation and fusion of skeletal myoblasts, and its expression is dramatically up-regulated in many cancer cells. While the extracellular portion of ADAM 12 contains an active metalloprotease and a cell-adhesion domain, the function of the cytoplasmic portion is much less clear. In this paper, we show that the cytoplasmic tail of ADAM 12 mediates interactions with the non-receptor protein tyrosine kinase Src. The interaction is direct, specific, and involves the N-terminal proline-rich region in the cytoplasmic tail of ADAM 12 and the Src homology 3 (SH3) domain of Src. ADAM 12 and Src co-immunoprecipitate from transfected C2C12 cells, suggesting that the two proteins form a complex in vivo. Co-expression of Src and ADAM 12, but not ADAM 9, in C2C12 cells results in activation of the recombinant Src. Moreover, endogenous ADAM 12 associates with and activates endogenous Src in differentiating C2C12 cells. These results indicate that ADAM 12 may mediate adhesion-induced signalling during myoblast differentiation.