Xia Xiaobo, Carnahan Robert H, Vaughan Meredith H, Wildenberg Gregg A, Reynolds Albert B
Department of Cancer Biology, Vanderbilt University Medical Center, 771 Preston Research Building, Nashville, TN 37232, USA.
Exp Cell Res. 2006 Oct 15;312(17):3336-48. doi: 10.1016/j.yexcr.2006.07.007. Epub 2006 Jul 25.
p120-catenin (p120) regulates cadherin turnover and is required for cadherin stability. Extensive and dynamic phosphorylation on tyrosine, serine and threonine residues in the N-terminal regulatory domain has been postulated to regulate p120 function, possibly through modulation of the efficiency of p120/cadherin interaction. Here we have utilized novel phospho-specific monoclonal antibodies to four major p120 serine and threonine phosphorylation sites to monitor individual phosphorylation events and their consequences. Surprisingly, membrane-localization and not cadherin interaction is the main determinant in p120 serine and threonine phosphorylation and dephosphorylation. Furthermore, the phospho-status of these four residues had no obvious effect on p120's role in cadherin complex stabilization or cell-cell adhesion. Interestingly, dephosphorylation was dramatically induced by PKC activation, but PKC-independent pathways were also evident. The data suggest that p120 dephosphorylation at these sites is modulated by multiple cell surface receptors primarily through PKC-dependent pathways, but these changes do not seem to reduce p120/cadherin affinity.
p120连环蛋白（p120）调节钙黏蛋白的周转，是钙黏蛋白稳定性所必需的。据推测，N端调节域中酪氨酸、丝氨酸和苏氨酸残基上广泛而动态的磷酸化可调节p120的功能，可能是通过调节p120/钙黏蛋白相互作用的效率来实现的。在这里，我们利用针对四个主要p120丝氨酸和苏氨酸磷酸化位点的新型磷酸特异性单克隆抗体来监测单个磷酸化事件及其后果。令人惊讶的是，膜定位而非钙黏蛋白相互作用是p120丝氨酸和苏氨酸磷酸化及去磷酸化的主要决定因素。此外，这四个残基的磷酸化状态对p120在钙黏蛋白复合体稳定或细胞间黏附中的作用没有明显影响。有趣的是，PKC激活可显著诱导去磷酸化，但不依赖PKC的途径也很明显。数据表明，这些位点的p120去磷酸化主要通过依赖PKC的途径由多种细胞表面受体调节，但这些变化似乎并未降低p120/钙黏蛋白的亲和力。
