AKAP-Lbc anchors protein kinase A and nucleates Gα12-selective Rho-mediated stress fiber formation
AKAP-Lbc anchors protein kinase A and nucleates Gα12-selective Rho-mediated stress fiber formation
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DOI：
10.1074/jbc.m106629200
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发表时间：
2001-11-23
影响因子：
4.8
通讯作者：
Scott, JD
中科院分区：
文献类型：
--
作者：
Diviani, D;Soderling, J;Scott, JD
DBL家族的鸟嘌呤核苷酸交换因子将信号从膜受体传递到Rho家族GTP酶。我们现在证明，LBC基因的一个较长的转录本编码一个嵌合分子，我们称之为AKAP-LBC，其功能是A-激酶锚定蛋白(AKAP)和Rho选择性鸟氨酸核苷酸交换因子。AKAP-LBC在成纤维细胞中的表达以Rho依赖的方式促进应激纤维的形成。应用溶血磷脂酸或选择性表达Gα(12)可增强细胞AKAP-LBC的激活。此外，生化研究表明，AKAP-LBC作为一种接头蛋白，选择性地将Gα(12)与Rho偶联。因此，AKAP-LBC锚定PKA并组装Rho介导的信号通路。
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 G alpha (12) enhances cellular AKAP-Lbc activation. Furthermore, biochemical studies indicate that AKAP-Lbc functions as an adaptor protein to selectively couple G alpha (12) to Rho. Thus, AKAP-Lbc anchors PKA and nucleates the assembly of a Rho-mediated signaling pathway.