Klingelhöfer Jörg, Troyanovsky Regina B, Laur Oscar Y, Troyanovsky Sergey
Division of Dermatology, Washington University Medical School, St Louis, MO 63110, USA.
Oncogene. 2003 Feb 27;22(8):1181-8. doi: 10.1038/sj.onc.1206245.
beta-Catenin is an intracellular multifunctional protein. In complex with the transmembrane adhesive receptor E-cadherin, it becomes plasma membrane-associated and mediates intercellular adhesion. A cytosolic pool of beta-catenin interacts with DNA-binding proteins and participates in signal transduction. To reveal the possible cross-talk between these two pools, we studied whether beta-catenin is exchanged between its free and cadherin-bound states. We found that pulse-labeled beta-catenin replaces the beta-catenin bound to the cell surface prebiotinylated E-cadherin immediately after synthesis. Approximately 25% of all pulse-labeled beta-catenin destined for E-cadherin associates with this protein via this mechanism. The rest of the newly synthesized beta-catenin arrives at the plasma membrane in a complex with the E-cadherin precursor. Immediately after arrival, this beta-catenin pool is transferred to the prebiotinylated E-cadherin. beta-Catenin released from E-cadherin may participate in new exchange cycles. This beta-catenin exchange is strongly affected in cells that contain mutations in the tumor suppressor gene APC. This process may contribute significantly to both cell-cell adhesion and beta-catenin-dependent signaling.
β-连环蛋白是一种细胞内多功能蛋白。与跨膜黏附受体E-钙黏蛋白结合后，它与质膜相关联并介导细胞间黏附。细胞质中的β-连环蛋白池与DNA结合蛋白相互作用并参与信号转导。为了揭示这两个池之间可能存在的相互作用，我们研究了β-连环蛋白是否在其游离状态和与钙黏蛋白结合的状态之间交换。我们发现，脉冲标记的β-连环蛋白在合成后立即取代了与细胞表面预生物素化的E-钙黏蛋白结合的β-连环蛋白。所有注定与E-钙黏蛋白结合的脉冲标记的β-连环蛋白中，约25%通过这种机制与该蛋白结合。其余新合成的β-连环蛋白与E-钙黏蛋白前体形成复合物到达质膜。到达后，这部分β-连环蛋白池立即转移到预生物素化的E-钙黏蛋白上。从E-钙黏蛋白释放的β-连环蛋白可能参与新的交换循环。在肿瘤抑制基因APC发生突变的细胞中，这种β-连环蛋白交换受到强烈影响。这一过程可能对细胞间黏附和β-连环蛋白依赖性信号传导都有显著贡献。
