Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction

Amy E. Hanlon Newell, Sarah E. Fiedler, Jenny M. Ruan, Jieyan Pan, P. Jeremy Wang, Jutta Deininger, Christopher L. Corless, Daniel W. Carr

Research output: Contribution to journalArticle

39 Scopus 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.

Original languageEnglish (US)
Pages (from-to)539-552
Number of pages14
JournalCell Motility and the Cytoskeleton
Volume65
Issue number7
DOIs
StatePublished - Jul 1 2008

Keywords

  • CABYR
  • Cilia
  • PKA
  • ROPN1
  • ROPN1L
  • SP17

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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