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首页> 外文期刊>The Journal of biological chemistry >A-Kinase Anchoring Protein (AKAP)-Lbc Anchors a PKN-based Signaling Complex Involved in α1-Adrenergic Receptor-induced p38 Activation
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A-Kinase Anchoring Protein (AKAP)-Lbc Anchors a PKN-based Signaling Complex Involved in α1-Adrenergic Receptor-induced p38 Activation

机译：A-kinase锚定蛋白（akap）-1bc锚定涉及α1-肾上腺素能受体诱导的p38活化的PKN的信号复合物

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The mitogen-activated protein kinases (MAPKs) pathways are highly organized signaling systems that transduce extracellular signals into a variety of intracellular responses. In this context, it is currently poorly understood how kinases constituting these signaling cascades are assembled and activated in response to receptor stimulation to generate specific cellular responses. Here, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critically involved in the activation of the p38α MAPK downstream of α1b-adrenergic receptors (α1b-ARs). Our results indicate that AKAP-Lbc can assemble a novel transduction complex containing the RhoA effector PKNα, MLTK, MKK3, and p38α, which integrates signals from α1b-ARs to promote RhoA-dependent activation of p38α. In particular, silencing of AKAP-Lbc expression or disrupting the formation of the AKAP-Lbc·p38α signaling complex specifically reduces α1-AR-mediated p38α activation without affecting receptor-mediated activation of other MAPK pathways. These findings provide a novel mechanistic hypothesis explaining how assembly of macromolecular complexes can specify MAPK signaling downstream of α1-ARs.
机译：丝裂原激活的蛋白激酶（MAPK）途径是高度有组织的信号传导系统，其将细胞外信号转化为各种细胞内反应。在这种情况下，目前尚未理解构成这些信号传导级联的激酶响应于受体刺激而被组装和激活，以产生特异性细胞反应。这里，我们表明AKAP-LBC是具有内在rho特异性的鸟嘌呤核苷酸交换因子活性的A-kinase锚定蛋白（Akap）是α1B-肾上腺素能受体下游P38αMapk的激活（α1b-ars ）。我们的结果表明，AKAP-LBC可以组装含有RHOA效应PKNα，MLTK，MKK3和P38α的新型转导络合物，其整合来自α1B-AR的信号，以促进P38α的RHOA依赖性激活。特别地，Akap-LBC表达的沉默或破坏AKAP-LBC·P38α信号传染性复合物的形成特异性降低了α1-AR介导的P38α活化，而不影响受体介导的其他MAPK途径的活化。这些发现提供了一种新的机制假设，说明了大分子复合物的组装如何在α1-ar下游指定MAPK信号传导。

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