Adhesion signaling by a novel mitotic substrate of src kinases
Adhesion signaling by a novel mitotic substrate of src kinases
复制标题
DOI：
10.1038/sj.onc.1208582
复制
发表时间：
2005-08-11
期刊：
影响因子：
8
通讯作者：
Moasser, MM
中科院分区：
文献类型：
--
作者：
Bhatt, AS;Erdjument-Bromage, H;Moasser, MM
在有丝分裂过程中，SRC激酶被激活并重新定位到细胞质中，但它们的有丝分裂功能仍然难以捉摸。我们在这里描述了一种新的src激酶有丝分裂底物。TraskI型跨膜糖蛋白是一种140 kDa的跨膜糖蛋白，与目前已知的蛋白家族无关。SRC在体外磷酸化TrASK，并在体内介导其有丝分裂过度磷酸化。TrASK与yes和src结合，间期定位于细胞膜，有丝分裂时进行细胞质再定位。TrASK的过表达导致细胞变圆和黏附表型的丧失。与细胞黏附功能一致，Trask1与许多黏附和基质蛋白相互作用，包括钙粘附素、合成酶和膜型丝氨酸蛋白酶1(MT-SP1)，并被MT-SP1蛋白水解性切割。TrASK在细胞黏附分子中是独一无二的，因为它处于细胞周期调节之下，因此将src激酶与细胞黏附的有丝分裂调节联系在一起。这提示了一条潜在的途径，即肿瘤中高活性的src激酶可以解除对黏附信号的调节，并介导转移表型。
Src kinases are activated and relocalize to the cytoplasm during mitosis, but their mitotic function has remained elusive. We describe here a novel mitotic substrate of src kinases. Trask (transmembrane and associated with src kinases) is a 140 kDa type I transmembrane glycoprotein unrelated to currently known protein families. Src kinases phosphorylate Trask in vitro and mediate its mitotic hyperphosphorylation in vivo. Trask associates with both yes and src, is localized to the cell membrane during interphase, and undergoes cytoplasmic relocalization during mitosis. Overexpression of Trask leads to cell rounding and a loss of adhesion phenotype. Consistent with a function in cell adhesion, Trask interacts with a number of adhesion and matrix proteins including cadherins, syndecans, and the membrane-type serine protease 1 (MT-SP1), and is proteolytically cleaved by MT-SP1. Trask is unique among cell adhesion molecules in that it is under cell cycle regulation and thus links src kinases with the mitotic regulation of cell adhesion. This suggests a potential pathway by which hyperactive src kinases in tumors can deregulate adhesion signaling and mediate the metastatic phenotype.