Haataja L, Groffen J, Heisterkamp N
Department of Pathology, Children's Hospital Los Angeles Research Institute and School of Medicine, University of Southern California, Los Angeles, California 90027, USA.
J Biol Chem. 1997 Aug 15;272(33):20384-8. doi: 10.1074/jbc.272.33.20384.
The small GTP-binding proteins Rac1 and Rac2 are critically important in regulating multiple signal transduction pathways in eukaryotic cells. Here we report the isolation of a novel third Rac family member, Rac3. Rac3 differs from Rac1/2 at its carboxyl-terminal end, a domain associated with subcellular localization and binding to specific cellular regulators. RAC3 mRNA expression patterns differ from those of RAC2, which is hematopoietic specific and also from those of RAC1. The RAC3 gene was mapped to chromosome 17q23-25, a region frequently deleted in breast cancer. Rac3 protein levels are not affected by organization of the actin cytoskeleton but remarkably, are serum-inducible. Rac3 is an active GTPase, and this activity is regulated by Bcr. When constitutively activated, Rac3 is able to stimulate efficiently the c-Jun amino-terminal kinase signaling pathway. These findings support a role for Rac3 in intracellular signaling.
小GTP结合蛋白Rac1和Rac2在调节真核细胞中的多种信号转导途径方面至关重要。在此，我们报告分离出一种新的Rac家族的第三个成员Rac3。Rac3在其羧基末端与Rac1/2不同，该结构域与亚细胞定位以及与特定细胞调节因子的结合有关。RAC3 mRNA的表达模式不同于造血特异性的RAC2，也不同于RAC1。RAC3基因定位于17q23 - 25染色体，该区域在乳腺癌中经常缺失。Rac3蛋白水平不受肌动蛋白细胞骨架组织的影响，但值得注意的是，它是血清诱导型的。Rac3是一种活性GTP酶，其活性受Bcr调节。当组成性激活时，Rac3能够有效刺激c-Jun氨基末端激酶信号通路。这些发现支持Rac3在细胞内信号传导中的作用。
