Martin-McCaffrey Luke, Hains Melinda D, Pritchard Grant A, Pajak Agnieszka, Dagnino Lina, Siderovski David P, D'Souza Sudhir J A
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Dev Dyn. 2005 Oct;234(2):438-44. doi: 10.1002/dvdy.20555.
Regulators of G-protein Signaling (RGS proteins) are a multigene family of GTPase-accelerating proteins for the Galpha subunit of heterotrimeric G-proteins. The mammalian R12 RGS protein subfamily is composed of RGS12 and RGS14, two proteins characterized by their multidomain architecture of hallmark RGS domain, tandem Ras-binding domains (RBDs), and a second Galpha interacting domain, the GoLoco motif. The Rgs12 gene generates multiple splice variants, the largest of which encodes N-terminal PDZ and PTB domains in addition to the core RGS/RBD/GoLoco motifs. The Rgs14 gene encodes a protein similar to the non-PDZ/PTB domain RGS12 splice variants. The spatiotemporal expression patterns of RGS12 and RGS14 proteins were examined by immunohistochemistry in a developmental series of postimplantation mouse embryo. We report that RGS12 splice variants exhibit differential spatiotemporal patterns of expression during postimplantation embryogenesis, suggesting nonoverlapping roles. In contrast, RGS14 is found ubiquitously throughout the postimplantation period. We conclude that R12 subfamily RGS proteins likely play significant and different roles in specific tissues and periods of mouse embryogenesis.
G蛋白信号调节因子(RGS蛋白)是异源三聚体G蛋白Gα亚基的GTP酶加速蛋白的多基因家族。哺乳动物R12 RGS蛋白亚家族由RGS12和RGS14组成,这两种蛋白的特征是具有标志性RGS结构域、串联Ras结合结构域(RBD)和第二个Gα相互作用结构域(GoLoco基序)的多结构域结构。Rgs12基因产生多种剪接变体,其中最大的变体除了核心RGS/RBD/GoLoco基序外,还编码N端PDZ和PTB结构域。Rgs14基因编码一种与非PDZ/PTB结构域RGS12剪接变体相似的蛋白质。通过免疫组织化学在植入后小鼠胚胎的发育系列中检测了RGS12和RGS14蛋白的时空表达模式。我们报告说,RGS12剪接变体在植入后胚胎发育过程中表现出不同的时空表达模式,表明其作用不重叠。相比之下,在整个植入后时期都普遍发现RGS14。我们得出结论,R12亚家族RGS蛋白可能在小鼠胚胎发育的特定组织和时期发挥重要且不同的作用。