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PMID:18421703

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Citation

Newell, AE, Fiedler, SE, Ruan, JM, Pan, J, Wang, PJ, Deininger, J, Corless, CL and Carr, DW (2008) Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction. Cell Motil. Cytoskeleton 65:539-52

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.

Links

PubMed Online version:10.1002/cm.20279

Keywords

A Kinase Anchor Proteins/genetics; A Kinase Anchor Proteins/metabolism; Amino Acid Sequence; Animals; Antigens, Surface/genetics; Antigens, Surface/metabolism; Calcium-Binding Proteins/genetics; Calcium-Binding Proteins/metabolism; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cilia/metabolism; Cilia/ultrastructure; Cyclic AMP/metabolism; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit/genetics; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit/metabolism; Female; Humans; Male; Membrane Proteins/genetics; Membrane Proteins/metabolism; Molecular Sequence Data; Phosphoproteins/genetics; Phosphoproteins/metabolism; Phylogeny; Protein Structure, Tertiary; Sequence Alignment; Sperm Tail/metabolism; Sperm Tail/ultrastructure; Tissue Distribution; rho GTP-Binding Proteins/genetics; rho GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CABYR

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CABYR

involved_in

GO:0003351: epithelial cilium movement involved in extracellular fluid movement

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CABYR

located_in

GO:0031514: motile cilium

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000066)

Seeded From UniProt

complete

HUMAN:AKAP3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96C74

F

Seeded From UniProt

complete

HUMAN:SP17

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SP17

involved_in

GO:0003351: epithelial cilium movement involved in extracellular fluid movement

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SP17

located_in

GO:0005929: cilium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SP17

located_in

GO:0031514: motile cilium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ROP1L

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75969

F

Seeded From UniProt

complete

HUMAN:ROP1L

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ROP1L

involved_in

GO:0003351: epithelial cilium movement involved in extracellular fluid movement

ECO:0000305: curator inference used in manual assertion

GO:0031514

P

Seeded From UniProt

complete

HUMAN:ROP1L

located_in

GO:0031514: motile cilium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ROP1A

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SP17

involved_in

GO:0003351: epithelial cilium movement

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SP17

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SP17

part_of

GO:0031514: motile cilium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SP17

part_of

GO:0005929: cilium

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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