Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA.
J Biol Chem. 2011 Nov 11;286(45):39269-81. doi: 10.1074/jbc.M111.277756. Epub 2011 Sep 2.
Cell movement requires the coordinated reception, integration, and processing of intracellular signals. We have discovered that the protein kinase A anchoring protein AKAP220 interacts with the cytoskeletal scaffolding protein IQGAP1 to influence cell motility. AKAP220/IQGAP1 networks receive and integrate calcium and cAMP second messenger signals and position signaling enzymes near their intended substrates at leading edges of migrating cells. IQGAP1 supports calcium/calmodulin-dependent association of factors that modulate microtubule dynamics. AKAP220 suppresses GSK-3β and positions this kinase to allow recruitment of the plus-end microtubule tracking protein CLASP2. Gene silencing of AKAP220 alters the rate of microtubule polymerization and the lateral tracking of growing microtubules and retards cell migration in metastatic human cancer cells. This reveals an unappreciated role for this anchored kinase/microtubule effector protein network in the propagation of cell motility.
细胞运动需要协调接收、整合和处理细胞内信号。我们发现蛋白激酶 A 锚定蛋白 AKAP220 与细胞骨架支架蛋白 IQGAP1 相互作用，影响细胞运动。AKAP220/IQGAP1 网络接收和整合钙和 cAMP 第二信使信号，并将信号酶定位在迁移细胞前缘的预期底物附近。IQGAP1 支持钙/钙调蛋白依赖性调节微管动力学的因子的结合。AKAP220 抑制 GSK-3β，并将该激酶定位，以允许募集正端微管追踪蛋白 CLASP2。AKAP220 的基因沉默改变微管聚合的速度和生长微管的侧向追踪，并在转移性人类癌细胞中减缓细胞迁移。这揭示了这种锚定激酶/微管效应蛋白网络在细胞运动传播中的一个未被重视的作用。
