Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205-2664, United States.
Life Sci. 2011 Apr 11;88(15-16):645-52. doi: 10.1016/j.lfs.2011.01.023. Epub 2011 Feb 2.
The Ras related GTPase Rap has been implicated in multiple cellular functions. A vital role for Rap GTPase in the cardiovasculature is emerging from recent studies. These small monomeric G proteins act as molecular switches, coupling extracellular stimulation to intracellular signaling through second messengers. This member of the Ras superfamily was once described as the transformation suppressor with the ability to ameliorate the Ras transformed phenotype; however, further studies uncovered a unique set of guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and effector proteins for Rap suggesting a more sophisticated role for this small GTPase. At least three different second messengers can activate Rap, namely cyclic AMP (cAMP), calcium and diacylglycerol. More recently, an investigation of Rap in the cardiovasculature has revealed multiple pathways of regulation involving Rap in this system. Two closely related isoforms of Rap1 exist, 1a and 1b. Murine genetic models exist for both and have been described. Although thought at first to be functionally redundant, these isoforms have differing roles in the cardiovasculature. The activation of Rap1a and 1b in various cell types of the cardiovasculature leads to alterations in cell attachment, migration and cell junction formation. This review will focus on the role of these Rap1 GTPases in hematopoietic, endothelial, smooth muscle, and cardiac myocyte function, and conclude with their potential role in human disease.
Ras 相关 GTP 酶 Rap 已被牵涉到多种细胞功能中。最近的研究表明，Rap GTP 酶在心血管系统中起着至关重要的作用。这些小分子单体 G 蛋白作为分子开关，通过第二信使将细胞外刺激与细胞内信号偶联。该 Ras 超家族成员曾被描述为具有转化抑制能力的转化抑制因子，能够改善 Ras 转化表型；然而，进一步的研究揭示了一组独特的鸟嘌呤核苷酸交换因子（GEF）、GTP 酶激活蛋白（GAP）和 Rap 的效应蛋白，表明这种小 GTP 酶具有更复杂的作用。至少有三种不同的第二信使可以激活 Rap，即环腺苷酸（cAMP）、钙和二酰基甘油。最近，对心血管系统中 Rap 的研究揭示了涉及该系统中 Rap 的多种调节途径。存在两种密切相关的 Rap1 同工型，1a 和 1b。两者都存在鼠基因模型，并已被描述。尽管最初认为它们在功能上是冗余的，但这些同工型在心血管系统中具有不同的作用。Rap1a 和 1b 在心血管系统的各种细胞类型中的激活导致细胞附着、迁移和细胞连接形成的改变。这篇综述将重点介绍这些 Rap1 GTP 酶在造血细胞、内皮细胞、平滑肌细胞和心肌细胞功能中的作用，并得出它们在人类疾病中的潜在作用。
