Identification and functional analysis of dual-specific A kinase-anchoring protein-2.
Since the cloning of dual-specificity A kinase-anchoring protein 2 (D-AKAP2), there has been considerable progress in understanding the structural features of this AKAP and its interaction with protein kinase A (PKA). The domain organization of D-AKAP2 is quite unique, containing two tandem, putative RGS domains, a PKA-binding motif, and a PDZ (PSD95/Dlg/ZO1)-binding motif. Although the function of D-AKAP2 has remained elusive, several reports suggest that D-AKAP2 is targeted to cotransporters in the kidney and that it may play a role in regulating transporter activity. In addition, the finding that a single nucleotide polymorphism in the PKA-binding region of D-AKAP2 may contribute to increased morbidity and mortality emphasizes the potential importance of this protein in pathogenesis. The first part of this article focuses on initial efforts to identify and clone D-AKAP2, followed by tissue localization and expression profiles. The latter half of the article focuses on the domain organization of D-AKAP2 and its interaction with PKA. Finally, a comprehensive analysis of the PKA binding motif is described, which has led to the development of novel peptides derived from D-AKAP2 that can be useful tools in probing the function of this AKAP in cellular and animal models.
Provid Pharmaceuticals, Piscataway, New Jersey 08854, USA.
L L
LL
Burns-Hamuro
D M
DM
Barraclough
S S
SS
Taylor
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003903:Deuterium / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D040081:Protein Array Analysis; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology
D054758:A Kinase Anchor Proteins; C484639:AKAP10 protein, human; D048868:Adaptor Proteins, Signal Transducing; D007527:Isoenzymes; D003903:Deuterium; D017868:Cyclic AMP-Dependent Protein Kinases