%0 Journal Article
%T AKAP5 and AKAP12 Form Homo-oligomers
%A Shujuan Gao
%A Hsien-yu Wang
%A Craig C Malbon
%J Journal of Molecular Signaling
%D 2011
%I Ubiquity Press
%R 10.1186/1750-2187-6-3
%X In gel analysis and sodium-dodecyl sulfate denaturation, AKAP12 behaved with a MW of a homo-dimer. Only in the presence of the chaotropic agent 8 M urea did gel analysis reveal a monomeric form of AKAP12. By separation by steric-exclusion chromatography, AKAP12 migrates with MW of ~840 kDa, suggestive of higher-order complexes such as a tetramer. Interestingly, the N-(1-840) and C-(840-1782) terminal regions of AKAP12 themselves retained the ability to form dimers, suggesting that the structural basis for the dimerization is not restricted to a single "domain" found within the molecule. In either sodium dodecyl sulfate or urea, AKAP5 displayed a relative mobility of a monomer, but by co-immunoprecipitation in native state was shown to oligomerize. When subjected to steric-exclusion chromatography, AKAP5 forms higher-order complexes with MW ~220 kDa, suggestive of tetrameric assemblies.Both AKAP5 and AKAP12 display the capacity to form supermolecular homo-oligomeric structures that likely influence the localization and function of these molecular scaffolds.Discovery of a docking site for the regulatory subunits (i.e., RI/RII) of cyclic AMP-dependent protein kinase A (PKA, A-kinase) was seminal in our understanding of the roles of A-kinase-anchoring protein (AKAP) scaffolds in cellular signaling [1-4]. AKAPs not only dock PKA, but act as molecular "tool boxes" that are multivalent and capable of docking other protein kinases (protein kinase C and the tyrosine kinase Src), phosphoprotein phosphatases, such as protein phosphatase 2B (PP2B) [5], cyclic AMP phosphodiesterases (PDE) [6-9], adaptor molecules [8-11], ion channels [12-14], and members of the superfamily of G protein-coupled receptors (GPCR) [15-17]. Two AKAPs, AKAP5 and AKAP12, that associate with the prototypic GPCR, the ¦Â2-adrenergic receptor (¦Â2-AR), have been the focus of intense research [16,18-21]. Herein, we examine these two members of the class of GPCR-associated AKAPs and explore the extent to which
%U http://www.jmolecularsignaling.com/content/6/1/3