Pivotal Role of AKAP12 in the Regulation of Cellular Adhesion Dynamics: Control of Cytoskeletal Architecture, Cell Migration, and Mitogenic Signaling.
Pivotal Role of AKAP12 in the Regulation of Cellular Adhesion Dynamics: Control of Cytoskeletal Architecture, Cell Migration, and Mitogenic Signaling.
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DOI：
10.1155/2012/529179
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Gelman IH
中科院分区：
文献类型：
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作者：
Akakura S;Gelman IH
细胞动力学由关键信号分子如cAMP依赖性蛋白激酶（PKA）和蛋白激酶C（PKC）控制。AKAP 12/SSeCKS/Gravin（AKAP 12）是PKA和PKC的支架蛋白，其以时空方式控制肌动蛋白-细胞骨架重组。AKAP 12还作为肿瘤抑制因子，调节细胞周期进程并抑制Src介导的致癌信号传导和细胞骨架途径。AKAP 12的再表达导致细胞扁平化、肌动蛋白细胞骨架的重组和正常化的粘着斑结构的产生。AKAP 12的下调诱导增厚的纵向应力纤维的形成和粘附复合物的增殖。AKAP 12-null小鼠胚胎成纤维细胞表现出PKC过度活化、细胞过早衰老和胞质分裂缺陷，这与AKAP 12导致PKC支架活性丧失有关。AKAP 12缺失小鼠表现出细胞衰老增加和对致癌物诱导的肿瘤发生的易感性增加。本文描述了AKAP 12的调节和支架功能，以及它如何调节细胞粘附，信号传导和致癌抑制。
Cellular dynamics are controlled by key signaling molecules such as cAMP-dependent protein kinase (PKA) and protein kinase C (PKC). AKAP12/SSeCKS/Gravin (AKAP12) is a scaffold protein for PKA and PKC which controls actin-cytoskeleton reorganization in a spatiotemporal manner. AKAP12 also acts as a tumor suppressor which regulates cell-cycle progression and inhibits Src-mediated oncogenic signaling and cytoskeletal pathways. Reexpression of AKAP12 causes cell flattening, reorganization of the actin cytoskeleton, and the production of normalized focal adhesion structures. Downregulation of AKAP12 induces the formation of thickened, longitudinal stress fibers and the proliferation of adhesion complexes. AKAP12-null mouse embryonic fibroblasts exhibit hyperactivation of PKC, premature cellular senescence, and defects in cytokinesis, relating to the loss of PKC scaffolding activity by AKAP12. AKAP12-null mice exhibit increased cell senescence and increased susceptibility to carcinogen-induced oncogenesis. The paper describes the regulatory and scaffolding functions of AKAP12 and how it regulates cell adhesion, signaling, and oncogenic suppression.