The SRC-associated protein CUB Domain-Containing Protein-1 regulates adhesion and motility.
The SRC-associated protein CUB Domain-Containing Protein-1 regulates adhesion and motility.
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DOI：
10.1038/onc.2011.262
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发表时间：
2012-02-02
期刊：
影响因子：
8
通讯作者：
Soltoff, S. P.
中科院分区：
文献类型：
--
作者：
Benes, C. H.;Poulogiannis, G.;Cantley, L. C.;Soltoff, S. P.
多个SRC家族激酶(SFK)在肿瘤中被普遍激活，并可能通过不完全了解的机制在肿瘤转移中发挥作用。最近的研究表明，CDCP1(Cub(补体C1r/C1s，Uegf，Bmp1)结构域蛋白-1)是一种跨膜蛋白，是一种可能参与肿瘤转移的SRC底物。在这里，我们显示，令人惊讶的是，SFK和CDCP1酪氨酸磷酸化的增加与FAK磷酸化的减少有关。这在人类肿瘤中似乎是正确的，正如我们对从正常和癌症肺组织样本中获得的亲和纯化的磷酸酪氨酸肽的质谱学数据集的相关性分析所显示的那样。在细胞培养中诱导CDCP1的酪氨酸磷酸化，包括由与其胞外区结合的单抗诱导，促进了sFK和FAK酪氨酸磷酸化的变化，以及与CDCP1相关的蛋白PKc™的变化，这些变化伴随着粘附性和运动性的增加。因此，在细胞系和人肺肿瘤中观察到的伴随CDCP1酪氨酸磷酸化的信号事件可能解释了CDCP1/SFK复合体是如何调节运动和黏附的。
Multiple SRC-family kinases (SFKs) are commonly activated in carcinoma and appear to have a role in metastasis through incompletely understood mechanisms. Recent studies have shown that CDCP1 (CUB (complement C1r/C1s, Uegf, Bmp1) Domain-Containing Protein-1) is a transmembrane protein and an SRC substrate potentially involved in metastasis. Here we show that increased SFK and CDCP1 tyrosine phosphorylation is, surprisingly, associated with a decrease in FAK phosphorylation. This appears to be true in human tumors as shown by our correlation analysis of a mass spectrometric data set of affinity-purified phosphotyrosine peptides obtained from normal and cancer lung tissue samples. Induction of tyrosine phosphorylation of CDCP1 in cell culture, including by a mAb that binds to its extracellular domain, promoted changes in SFK and FAK tyrosine phosphorylation, as well as in PKC™, a protein known to associate with CDCP1, and these changes are accompanied by increases in adhesion and motility. Thus, signaling events that accompany the CDCP1 tyrosine phosphorylation observed in cell lines and human lung tumors may explain how the CDCP1/SFK complex regulates motility and adhesion.
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影响因子：
3.9
作者：
Courtneidge, SA
通讯作者：
Courtneidge, SA
影响因子：
8
作者：
Bhatt, AS;Erdjument-Bromage, H;Moasser, MM
通讯作者：
Moasser, MM
影响因子：
4.8
作者：
He, Yaowu;Wortmann, Andreas;Hooper, John D.
通讯作者：
Hooper, John D.
影响因子：
6.2
作者：
Allgayer, H;Boyd, DD;Gallick, GE
通讯作者：
Gallick, GE
DOI：
10.1073/pnas.84.8.2251
发表时间：
1987-04-01
影响因子：
11.1
作者：
BOLEN, JB;VEILLETTE, A;ROSEN, N
通讯作者：
ROSEN, N