A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling complex involved in alpha1-adrenergic receptor-induced p38 activation.
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Cariolato L, Cavin S, Diviani D
A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling complex involved in alpha1-adrenergic receptor-induced p38 activation.
J Biol Chem. 2011 Mar 11;286(10):7925-37. doi: 10.1074/jbc.M110.185645. Epub 2011 Jan 11.
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- 21224381 [ View in PubMed]
- Abstract
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 p38alpha MAPK downstream of alpha(1b)-adrenergic receptors (alpha(1b)-ARs). Our results indicate that AKAP-Lbc can assemble a novel transduction complex containing the RhoA effector PKNalpha, MLTK, MKK3, and p38alpha, which integrates signals from alpha(1b)-ARs to promote RhoA-dependent activation of p38alpha. In particular, silencing of AKAP-Lbc expression or disrupting the formation of the AKAP-Lbc.p38alpha signaling complex specifically reduces alpha(1)-AR-mediated p38alpha 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 alpha(1)-ARs.