Tachibana K, Sato T, D'Avirro N, Morimoto C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Exp Med. 1995 Oct 1;182(4):1089-99. doi: 10.1084/jem.182.4.1089.
Focal adhesion kinase (pp125FAK) is localized to focal adhesions and tyrosine phosphorylated by the engagement of beta 1 integrins. However, it is unclear how pp125FAK is linked to integrin molecules. We demonstrate that pp125FAK is directly associated with paxillin, a 68-kD cytoskeleton protein. The COOH-terminal domain of pp125FAK spanning FAK residues 919-1042 is sufficient for paxillin binding and has vinculin-homologous amino acids, which are essential for paxillin binding. Microinjection and subsequent immunohistochemical analysis reveal that glutathione S-transferase-FAK fusion proteins, which bind to paxillin, localize to focal adhesions, whereas fusion proteins with no paxillin-binding activity do not localize to focal adhesions. These findings strongly suggest that pp125FAK is localized to focal adhesions by the direct association with paxillin.
粘着斑激酶(pp125FAK)定位于粘着斑,并通过β1整合素的结合而发生酪氨酸磷酸化。然而,尚不清楚pp125FAK如何与整合素分子相连。我们证明pp125FAK与桩蛋白(一种68-kD的细胞骨架蛋白)直接相关。pp125FAK跨越FAK残基919 - 1042的COOH末端结构域足以与桩蛋白结合,并且具有与纽蛋白同源的氨基酸,这对于桩蛋白结合至关重要。显微注射及随后的免疫组织化学分析显示,与桩蛋白结合的谷胱甘肽S - 转移酶 - FAK融合蛋白定位于粘着斑,而没有桩蛋白结合活性的融合蛋白则不定位于粘着斑。这些发现有力地表明,pp125FAK通过与桩蛋白的直接关联而定位于粘着斑。