G-Protein-coupled receptor-associated A-kinase anchoring proteins: AKAP79 and AKAP250 (gravin).
A-kinase anchoring proteins (AKAPs) define an expanding group of scaffold proteins that display a signature binding site for the RI/RII subunit of protein kinase A. AKAPs are multivalent and a subset of these scaffold proteins also display the ability to associate with the prototypic member of G-protein-coupled receptors, the beta(2)-adrenergic receptor. Both AKAP79 (also known as AKAP5) and AKAP250 (also known as gravin or AKAP12) have been shown to associate with the beta(2)-adrenergic receptor, but each directs downstream signaling events in decidedly different manners. The primary structures, common and unique protein motifs are of interest. Both proteins display largely natively unfolded primary sequences that provide a necklace on which short, structured regions of sequence are found. Membrane association appears to involve both interactions with the lipid bilayer via docking to a G-protein-coupled receptor as well as interactions of short positively charged domains with the inner leaflet of the cell membrane. Gravin, unlike AKAP79, displays a canonical site at its N-terminus that is subject to N-myristoylation. AKAP79 appears to function in switching signaling pathways of the receptor from adenylylcyclase to activation of the mitogen-activated protein kinase cascade. Gravin, in contrast, is essential for the resensitization and recycling of the receptors following agonist-induced activation, desensitization, and internalization. Each AKAP provides a template that enables space-time continuum features to G-protein-coupled signaling pathways as well as a paradigm for explaining apparent compartmentalization of cell signaling.
Wang
Hsien-Yu
HY
Department of Physiology & Biophysics, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA.
Tao
Jiangchuan
J
Shumay
Elena
E
Malbon
Craig C
CC
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D017510:Protein Folding; D011506:Proteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction; D040681:Structural Homology, Protein
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; C487775:AKAP5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled