Diviani D, Soderling J, Scott J D
Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
J Biol Chem. 2001 Nov 23;276(47):44247-57. doi: 10.1074/jbc.M106629200. Epub 2001 Sep 6.
Guanine nucleotide exchange factors of the Dbl family relay signals from membrane receptors to Rho family GTPases. We now demonstrate that a longer transcript of the Lbc gene encodes a chimeric molecule, which we have called AKAP-Lbc, that functions as an A-kinase-anchoring protein (AKAP) and a Rho-selective guanine nucleotide exchange factor. Expression of AKAP-Lbc in fibroblasts favors the formation of stress fibers in a Rho-dependent manner. Application of lysophosphatidic acid or selective expression of Galpha(12) enhances cellular AKAP-Lbc activation. Furthermore, biochemical studies indicate that AKAP-Lbc functions as an adaptor protein to selectively couple Galpha(12) to Rho. Thus, AKAP-Lbc anchors PKA and nucleates the assembly of a Rho-mediated signaling pathway.
Dbl家族的鸟嘌呤核苷酸交换因子将信号从膜受体传递至Rho家族GTP酶。我们现在证明,Lbc基因的一个较长转录本编码一种嵌合分子,我们将其称为AKAP-Lbc,它作为一种A激酶锚定蛋白(AKAP)和一种Rho选择性鸟嘌呤核苷酸交换因子发挥作用。AKAP-Lbc在成纤维细胞中的表达以Rho依赖的方式促进应力纤维的形成。溶血磷脂酸的应用或Gα12的选择性表达增强细胞内AKAP-Lbc的激活。此外,生化研究表明,AKAP-Lbc作为一种衔接蛋白,将Gα12与Rho选择性偶联。因此,AKAP-Lbc锚定PKA并促使Rho介导的信号通路组装。