Networking with AKAPs

AKAP-Lbc integrates multiple signaling pathways. GPCRs such as M1 muscarinic receptor (M1-R) initiate a signaling cascade involving PKC-mediated activation of PKD and phosphorylation of HDAC in the nucleus. In another pathway, Gα12-coupled receptors such as the lysophospholipid receptor (LPA-R) stimulate the intrinsic Rho-GEF activity of AKAP-Lbc. When cAMP concentrations are low (top panel), PKD activity is relatively low and Rho-GEF activity relatively high. Gαs-coupled receptors such as βAR stimulate production of cAMP (orange cloud) by adenylyl cyclases (bottom panel), leading to the activation of PKA. Phosphorylation of AKAP-Lbc by PKA accentuates PKD signaling and curtails Rho-GEF activity. For simplicity, both panels show conditions where Gαq/11 and Gα12 pathways are active. HDAC, histone deacetylase; LPA-R, Lysophosphatidic acid receptor; βAR, beta-adrenergic receptor; LC3, microtubule associated protein light chain 3.