Scheswohl Danielle M, Harrell Jessica R, Rajfur Zenon, Gao Guanghua, Campbell Sharon L, Schaller Michael D
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
J Mol Signal. 2008 Jan 2;3:1. doi: 10.1186/1750-2187-3-1.
FAK localization to focal adhesions is essential for its activation and function. Localization of FAK is mediated through the C-terminal focal adhesion targeting (FAT) domain. Recent structural analyses have revealed two paxillin-binding sites in the FAT domain of FAK. To define the role of paxillin binding to each site on FAK, point mutations have been engineered to specifically disrupt paxillin binding to each docking site on the FAT domain of FAK individually or in combination.
These mutants have been characterized and reveal an important role for paxillin binding in FAK subcellular localization and signaling. One paxillin-binding site (comprised of alpha-helices 1 and 4 of the FAT domain) plays a more prominent role in localization than the other. Mutation of either paxillin-binding site has similar effects on FAK activation and downstream signaling. However, the sites aren't strictly redundant as each mutant exhibits phosphorylation/signaling defects distinct from wild type FAK and a mutant completely defective for paxillin binding.
The studies demonstrate that the two paxillin-binding sites of FAK are not redundant and that both sites are required for FAK function.
粘着斑激酶（FAK）定位于粘着斑对于其激活和功能至关重要。FAK的定位是通过C端粘着斑靶向（FAT）结构域介导的。最近的结构分析揭示了FAK的FAT结构域中有两个桩蛋白结合位点。为了确定桩蛋白与FAK上每个位点结合的作用，已设计出点突变，以特异性破坏桩蛋白分别或联合与FAK的FAT结构域上每个对接位点的结合。
这些突变体已得到表征，并揭示了桩蛋白结合在FAK亚细胞定位和信号传导中的重要作用。一个桩蛋白结合位点（由FAT结构域的α螺旋1和4组成）在定位中比另一个发挥更突出的作用。任一桩蛋白结合位点的突变对FAK激活和下游信号传导具有相似的影响。然而，这些位点并非完全冗余，因为每个突变体都表现出与野生型FAK不同的磷酸化/信号缺陷，以及一个对桩蛋白结合完全有缺陷的突变体。
研究表明，FAK的两个桩蛋白结合位点并非冗余，且两个位点对于FAK功能都是必需的。
