AKAP (A-kinase anchoring protein) domains: beads of structure-function on the necklace of G-protein signalling.
AKAPs (A-kinase anchoring proteins) are members of a diverse family of scaffold proteins that minimally possess a characteristic binding domain for the RI/RII regulatory subunit of protein kinase A and play critical roles in establishing spatial constraints for multivalent signalling assemblies. Especially for G-protein-coupled receptors, the AKAPs provide an organizing centre about which various protein kinases and phosphatases can be assembled to create solid-state signalling devices that can signal, be modulated and trafficked within the cell. The structure of AKAP250 (also known as gravin or AKAP12), based on analyses of milligram quantities of recombinant protein expressed in Escherichia coli, suggests that the AKAP is probably an unordered scaffold, acting as a necklace on which 'jewels' of structure-function (e.g. the RII-binding domain) that provide docking sites on which signalling components can be assembled. Recent results suggest that AKAP250 provides not only a 'tool box' for assembling signalling elements, but may indeed provide a basis for spatial constraint observed for many signalling paradigms. The spatial dimension of the integration of cell signalling will probably reflect many functions performed by members of the AKAP family.
Malbon
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Department of Pharmacology, Diabetes & Metabolic Diseases Research Center, School of Medicine-HSC, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA. craig@pharm.sunysb.edu
Tao
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Shumay
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Wang
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D054758:A Kinase Anchor Proteins; D002352:Carrier Proteins / Q000737:chemistry*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D004926:Escherichia coli / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008051:Lipid Bilayers; D011506:Proteins; D011994:Recombinant Proteins; D011493:Protein Kinase C; D019204:GTP-Binding Proteins