title: Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction.
abstract: A-kinase anchoring proteins (AKAPs) bind to protein kinase A (PKA) via an amphipathic helix domain that interacts with a dimerization/docking domain on the regulatory (R) subunit of PKA. Four other mammalian proteins (ROPN1, ASP, SP17, and CABYR) also contain a highly conserved RII dimerization/docking (R2D2) domain, suggesting all four proteins may interact with all AKAPs in a manner similar to RII. All four of these proteins were originally detected in the flagellum of mammalian sperm. In this report, we demonstrate that all four R2D2 proteins are expressed in a wide variety of tissues and three of the proteins SP17, CABYR, and ASP are located in motile cilia of human bronchus and fallopian tubes. In addition, we detect SP17 in primary cilia. We also provide evidence that ROPN1 and ASP bind to a variety of AKAPs and this interaction can be disrupted with anchoring inhibitor peptides. The interaction of SP17 and CABYR with AKAPs appears to be much more limited. None of the R2D2 proteins appears to bind cAMP, a fundamental characteristic of the regulatory subunits of PKA. These observations suggest that R2D2 proteins utilize docking interactions with AKAPs to accomplish their function of regulating cilia and flagella. Based on location, affinity for AKAPs and lack of affinity for cAMP, it appears that each R2D2 protein has a unique role in this process.
authors.affiliation: VA Medical Center and Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Amy E Hanlon
authors.initials: AE
authors.lastname: Newell
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Fiedler
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Ruan
authors.forename: Jieyan
authors.initials: J
authors.lastname: Pan
authors.forename: P Jeremy
authors.initials: PJ
authors.lastname: Wang
authors.forename: Jutta
authors.initials: J
authors.lastname: Deininger
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Carr
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013082:Sperm Tail / Q000378:metabolism / Q000648:ultrastructure; D014018:Tissue Distribution; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D054758:A Kinase Anchor Proteins; D000954:Antigens, Surface; C448922:CABYR protein, human; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D008565:Membrane Proteins; D010750:Phosphoproteins; C404565:ROPN1 protein, human; C090172:SPA17 protein, human; D000242:Cyclic AMP; D020741:rho GTP-Binding Proteins