Faculty Collaboration Database

Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction. Cell Motil Cytoskeleton 2008 Jul;65(7):539-52

Date

04/19/2008

Pubmed ID

18421703

DOI

10.1002/cm.20279

Scopus ID

2-s2.0-46849104056 (requires institutional sign-in at Scopus site)   47 Citations

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.

Author List

Newell AE, Fiedler SE, Ruan JM, Pan J, Wang PJ, Deininger J, Corless CL, Carr DW

Author

Jutta Deininger DNP APP Hybrid in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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