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PMID: 12475942 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Characterization of an A-kinase anchoring protein in human ciliary axonemes.

Molecular biology of the cell ·Vol. 13 ·No. 12 ·2002-12-00 ·Pages 4156-66

Kultgen PL, Byrd SK, Ostrowski LE, Milgram SL

Abstract

Although protein kinase A (PKA) activation is known to increase ciliary beat frequency in humans the molecular mechanisms involved are unknown. We demonstrate that PKA is associated with ciliary axonemes where it specifically phosphorylates a 23-kDa protein. Because PKA is often localized to subcellular compartments in proximity to its substrate(s) via interactions with A-kinase-anchoring proteins (AKAPs), we investigated whether an AKAP was also associated with ciliary axonemes. This study has identified a novel 28 kDa AKAP (AKAP28)that is highly enriched in airway axonemes. The mRNA for AKAP28 is up-regulated as primary airway cells differentiate and is specifically expressed in tissues containing cilia and/or flagella. Additionally, both Western blot and immunostaining data show that AKAP28 is enriched in airway cilia. These data demonstrate that we have identified the first human axonemal AKAP, a protein that likely plays a role in the signaling necessary for efficient modulation of ciliary beat frequency.

MeSH Terms
A Kinase Anchor Proteins Adaptor Proteins, Signal Transducing Adenoviridae/genetics Amino Acid Sequence Axons/metabolism Binding Sites Blotting, Northern Bronchi/cytology Carrier Proteins/chemistry,metabolism Cells, Cultured Cilia/metabolism Cloning, Molecular Cyclic AMP-Dependent Protein Kinases/chemistry,metabolism DNA, Complementary/metabolism Epithelial Cells/metabolism Gene Library Genetic Vectors Glutathione Transferase/metabolism Green Fluorescent Proteins HeLa Cells Humans Immunoblotting Immunohistochemistry Luminescent Proteins/metabolism Membrane Proteins Molecular Sequence Data Precipitin Tests Protein Binding Recombinant Fusion Proteins/metabolism Sequence Homology, Amino Acid Time Factors Tissue Distribution
Chemicals
A Kinase Anchor Proteins AKAP14 protein, human Adaptor Proteins, Signal Transducing Carrier Proteins DNA, Complementary Luminescent Proteins Membrane Proteins Recombinant Fusion Proteins testis-specific A-kinase-anchoring-protein, rat Green Fluorescent Proteins Glutathione Transferase Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kultgen Patricia L
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Byrd Sherell K
Ostrowski Lawrence E
Milgram Sharon L
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-07-0391
Published
2002-12-00
Pages
4156-66
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC138623
Subset
IM
Grants
NHLBI NIH HHS · P50 HL060280 · United States
NHLBI NIH HHS · HL-34355 · United States
NHLBI NIH HHS · HL-60280 · United States
NHLBI NIH HHS · HL-63103 · United States
External Links
PubMed source DOI: 10.1091/mbc.e02-07-0391 PMC Full Text View journal details
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