Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility
文献类型：期刊论文
| 作者 | Wang, WQ; Liu, Y; Liao, K |
| 刊名 | BMC CELL BIOLOGY
 |
| 出版日期 | 2011 |
| 卷号 | 12期号:1页码:49-49 |
| 关键词 | cortactin cortactin tyrosine phosphorylation FAK FAK-Src complex focal adhesions cell motility |
| 通讯作者 | Liao, K (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,kliao@sibs.ac.cn |
| 英文摘要 | Background: Cell migration plays an important role in many physiological and pathological processes, including immune cell chemotaxis and cancer metastasis. It is a coordinated process that involves dynamic changes in the actin cytoskeleton and its interplay with focal adhesions. At the leading edge of a migrating cell, it is the rearrangement of actin and its attachment to focal adhesions that generates the driving force necessary for movement. However, the mechanisms involved in the attachment of actin filaments to focal adhesions are still not fully understood. Results: Signaling by the FAK-Src complex plays a crucial role in regulating the formation of protein complexes at focal adhesions to which the actin filaments are attached. Cortactin, an F-actin associated protein and a substrate of Src kinase, was found to interact with FAK through its SH3 domain and the C-terminal proline-rich regions of FAK. We found that the autophosphorylation of Tyr(397) in FAK, which is necessary for FAK activation, was not required for the interaction with cortactin, but was essential for the tyrosine phosphorylation of the associated cortactin. At focal adhesions, cortactin was phosphorylated at tyrosine residues known to be phosphorylated by Src. The tyrosine phosphorylation of cortactin and its ability to associate with the actin cytoskeleton were required in tandem for the regulation of cell motility. Cell motility could be inhibited by truncating the N-terminal F-actin binding domains of cortactin or by blocking tyrosine phosphorylation (Y421/466/475/482F mutation). In addition, the mutant cortactin phosphorylation mimic (Y421/466/475/482E) had a reduced ability to interact with FAK and promoted cell motility. The promotion of cell motility by the cortactin phosphorylation mimic could also be inhibited by truncating its N-terminal F-actin binding domains. Conclusions: Our results suggest that cortactin acts as a bridging molecule between actin filaments and focal adhesions. The cortactin N-terminus associates with F-actin, while its C-terminus interacts with focal adhesions. The tyrosine phosphorylation of cortactin by the FAK-Src complex modulates its interaction with FAK and increases its turnover at focal adhesions to promote cell motility. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | GROWTH-FACTOR ; FAMILY KINASES ; ACTIN ; MIGRATION ; SUBSTRATE ; PROMOTES ; INVASION ; AUTOPHOSPHORYLATION ; CYTOSKELETON ; PP60(SRC) |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000298171300001 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/902]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Wang, WQ,Liu, Y,Liao, K. Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility[J]. BMC CELL BIOLOGY,2011,12(1):49-49. |
| APA | Wang, WQ,Liu, Y,&Liao, K.(2011).Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility.BMC CELL BIOLOGY,12(1),49-49. |
| MLA | Wang, WQ,et al."Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility".BMC CELL BIOLOGY 12.1(2011):49-49. |
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