Down-regulation of the filamentous actin cross-linking activity of cortactin by src-mediated tyrosine phosphorylation
Down-regulation of the filamentous actin cross-linking activity of cortactin by src-mediated tyrosine phosphorylation
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DOI：
10.1074/jbc.272.21.13911
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发表时间：
1997-05-23
影响因子：
4.8
通讯作者：
Zhan, X
中科院分区：
文献类型：
--
作者：
Huang, C;Ni, YS;Zhan, X
Corpine是pp 60（c-src）的主要底物，是一种丝状肌动蛋白（F-actin）结合蛋白。在这里，我们表明，coronin可以促进沉降的F-肌动蛋白在离心力下，F-肌动蛋白是否则无法沉淀。负染色后的电子显微镜分析进一步显示，肌动蛋白丝在coronin的存在下交联成不同程度的厚度的束。因此，Cordiform也是一种F-肌动蛋白交联蛋白。我们还表明，最佳的F-肌动蛋白的交联活性coronin需要在7.3-7.5的范围内的生理pH值。此外，pp 60（c-src）在体外磷酸化coronin，导致其F-肌动蛋白交联活性以依赖于酪氨酸磷酸化水平的方式显著降低。此外，pp 60（c-src）适度抑制coronin的F-肌动蛋白结合活性。这项研究提出了第一个证据表明，pp 60（c-src）可以直接调节其底物对细胞骨架的活性，并暗示了corneum作为酪氨酸激酶调节的细胞骨架重组中的F-肌动蛋白调节剂的作用。
Cortactin, a prominent substrate for pp60(c-src), is a filamentous actin (F-actin) binding protein. We show here that cortactin can promote sedimentation of F-actin at centrifugation forces under which F-actin is otherwise not able to be precipitated. Electron microscopic analysis after negative staining further revealed that actin filaments in the presence of cortactin are cross-linked into bundles of various degrees of thickness. Hence, cortactin is also an F-actin cross-linking protein. We also demonstrate that the optimal F-actin cross-linking activity of cortactin requires a physiological pH in a range of 7.3-7.5. Furthermore, pp60(c-src) phosphorylates cortactin in vitro, resulting in a dramatic reduction of its F-actin cross-linking activity in a manner depending on levels of tyrosine phosphorylation, In addition, pp60(c-src) moderately inhibits the F-actin binding activity of cortactin. This study presents the first evidence that pp60(c-src) can directly regulate the activity of its substrate toward the cytoskeleton and implies a role of cortactin as an F-actin modulator in tyrosine kinase-regulated cytoskeleton reorganization.