期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 12, 页码 2416-2429出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.184721
关键词
Cortactin; Adherens junction; Vinculin; Protein kinase D; PKD; Cadherin-1; CDH1; Epithelial cadherin; E-cadherin
类别
资金
- Deutsche Forschungsgemeinschaft (DFG) [EI792/3-1, SE 676/10-1, CRC 1149]
- Fonds Wetenschappelijk Onderzoek (FWO - Fund for Scientific Research Flanders)
- EU [259770]
Dynamic regulation of cell-cell adhesion by the coordinated formation and dissolution of E-cadherin-based adherens junctions is crucial for tissue homeostasis. The actin-binding protein cortactin interacts with E-cadherin and enables F-actin accumulation at adherens junctions. Here, we were interested to study the broader functional interactions of cortactin in adhesion complexes. In line with literature, we demonstrate that cortactin binds to E-cadherin, and that a posttranslational modification of cortactin, RhoA-induced phosphorylation by protein kinase D1 (PKD1; also known as PRKD1) at S298, impairs adherens junction assembly and supports their dissolution. Two new S298-phosphorylation-dependent interactions were also identified, namely, that phosphorylation of cortactin decreases its interaction with beta-catenin and the actin-binding protein vinculin. In addition, binding of vinculin to beta-catenin, as well as linkage of vinculin to F-actin, are also significantly compromised upon phosphorylation of cortactin. Accordingly, we found that regulation of cell-cell adhesion by phosphorylation of cortactin downstream of RhoA and PKD1 is vitally dependent on vinculin-mediated protein interactions. Thus, cortactin, unexpectedly, is an important integration node for the dynamic regulation of protein complexes during breakdown and formation of adherens junctions.
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