背景 | <p>IQGAPs are scaffolding proteins involved in mediating cytoskeletal function. They contain multiple protein interaction domains and bind to a growing number of molecules including actin, myosin light chain, calmodulin, E-cadherin, and β-catenin (reviewed in 1). Through their GAP-related domains, they bind the small GTPases Rac1 and cdc42. IQGAPs lack GAP activity, however, and regulate small GTPases by stabilizing their GTP-bound (active) forms (2,3). Research studies have shown that the function and distribution of the IQGAP proteins widely vary. IQGAP1 is ubiquitously expressed and has been found to interact with APC (4) and the CLIP170 complex (5) in response to small GTPases, promoting cell polarization and migration. Additional research studies have suggested that IQGAP1 could play a part in the invasiveness of some cancers (6-8). IQGAP2, which is about 60% identical to IQGAP1, is expressed primarily in liver (3), but lower levels have been detected in the prostate, kidney, thyroid, stomach, and testis (9,10). Research studies have shown that IQGAP2 displays tumor suppressor properties (11). Less is known about the function of IQGAP3, but this protein is present in the lung, brain, small intestine, and testis (9) and is only expressed in proliferating cells (12), suggesting a role in cell growth and division.</p>IQGAPs是参与介导细胞骨架功能的支架蛋白。它们还有多个蛋白相互作用结构域,而且和逐渐增多的分子结合包括actin, myosin light chain, calmodulin, E-cadherin, 和β-catenin (reviewed in 1).通过它们的GAP相关结构域,它们能够和小GTPases Rac1 以及 cdc42结合。但IQGAPs缺乏Gap功能,能够通过稳定它们的GTP-结合(活化)形式而调节GTPases(2,3)。研究表明IQGAP的功能和表达分布差异很大。IQGAP1广泛表达并且被发现在小GTPases作业下可以和APC(4)和CLIP170复合物(5)结合,促进细胞极化和细胞迁移。更多的研究表明IQGAP1在某些癌症的侵润中也发挥了一定作用(6-8).IQGAP2,与IQGAP1有60%相似性,主要表达在肝脏中(3),前列腺,肾脏,甲状腺,胃和睾丸中也检测到了低水平的表达(9,10)。研究表明IQGAP2表现了抑癌能力(11)。对IQGAP3的研究较少,但是钙蛋白表达在飞,脑,小肠和睾丸中(9),也是唯一表达于增殖细胞中的该亚型(12),提示它可能在细胞生长和分裂中发挥了一定作用。 |