A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling complex involved in ?1-adrenergic receptor-induced p38 activation.

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 p38? MAPK downstream of ?(1b)-adrenergic receptors (?(1b)-ARs). Our results indicate that AKAP-Lbc can assemble a novel transduction complex containing the RhoA effector PKN?, MLTK, MKK3, and p38?, which integrates signals from ?(1b)-ARs to promote RhoA-dependent activation of p38?. In particular, silencing of AKAP-Lbc expression or disrupting the formation of the AKAP-Lbc·p38? signaling complex specifically reduces ?(1)-AR-mediated p38? 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 ?(1)-ARs.

SUBMITTER: Cariolato L 

PROVIDER: S-EPMC3048679 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature