Characterization of an A-kinase anchoring protein in human ciliary axonemes.
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, Amino Acid Sequence, Axons, Binding Sites, Blotting, Northern, Bronchi, Carrier Proteins, Cells, Cultured, Cilia, Cloning, Molecular, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, Epithelial Cells, Gene Library, Genetic Vectors, Glutathione Transferase, Green Fluorescent Proteins, Hela Cells, Humans, Immunoblotting, Immunohistochemistry, Luminescent Proteins, Membrane Proteins, Molecular Sequence Data, Precipitin Tests, Protein Binding, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Time Factors, Tissue Distribution
A Kinase Anchor Proteins, Adaptor Proteins, Signal Transducing, Adenoviridae, Amino Acid Sequence, Axons, Binding Sites, Blotting, Northern, Bronchi, Carrier Proteins, Cells, Cultured, Cilia, Cloning, Molecular, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, Epithelial Cells, Gene Library, Genetic Vectors, Glutathione Transferase, Green Fluorescent Proteins, Hela Cells, Humans, Immunoblotting, Immunohistochemistry, Luminescent Proteins, Membrane Proteins, Molecular Sequence Data, Precipitin Tests, Protein Binding, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Time Factors, Tissue Distribution
Mol. Biol. Cell
Date: Dec. 01, 2002
PubMed ID: 12475942
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