A-kinase-interacting protein localizes protein kinase A in the nucleus.
The genetic variability and covalent modifications associated with the amino terminus of the protein kinase A (PKA) catalytic (C) subunit suggest that it may contribute to protein-protein interactions and/or localization. By using a yeast two-hybrid screen, we identified a PKA-interacting protein (AKIP1) that binds to the amino terminus (residues 1-39) of the C subunit of PKA. The interaction was localized to the A helix (residues 14-39) of the C subunit and to the carboxyl terminus of AKIP1. AKIP1 thus defines the amino-terminal A helix of PKA as a protein interaction motif. In normal breast (Hs 578 Bst) and HeLa cells, AKIP1 is present in the nucleus as speckles. A nuclear localization signal (Arg-14 and Arg-15) was identified. Upon stimulation with forskolin, HeLa cells expressing AKIP1 accumulated higher levels of the endogenous C subunit in the nucleus. Deletion of the carboxyl terminus of AKIP1 or overexpression of residues 1-39 of the C subunit abolished nuclear localization of the activated endogenous C subunit. Thus, AKIP1 describes a PKA-interacting protein that can contribute to localization by a mechanism that is distinct from A-kinase anchoring proteins that interact with the regulatory subunits.
Sastri
Mira
M
The Howard Hughes Medical Institute and Departments of Chemistry and Biochemistry and Pharmacology, University of California at San Diego, La Jolla, CA 92093-0654, USA.
Barraclough
David M
DM
Carmichael
Peter T
PT
Taylor
Susan S
SS
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D021122:Protein Subunits; D021381:Protein Transport; D011506:Proteins
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D011506:Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D017868:Cyclic AMP-Dependent Protein Kinases