D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain.
Subcellular localization directed by specific A kinase anchoring proteins (AKAPs) is a mechanism for compartmentalization of cAMP-dependent protein kinase (PKA). Using a two-hybrid screen, a novel AKAP was isolated. Because it interacts with both the type I and type II regulatory subunits, it was defined as a dual specific AKAP ... or D-AKAP1. Here we report the cloning and characterization of another novel cDNA isolated from that screen. This new member of the D-AKAP family, D-AKAP2, also binds both types of regulatory subunits. A message of 5 kb pairs was detected for D-AKAP2 in all embryonic stages and in all adult tissues tested. In brain, skeletal muscle, kidney, and testis, a 10-kb mRNA was identified. In testis, several small mRNAs were observed. Therefore, D-AKAP2 represents a novel family of proteins. cDNA cloning from a mouse testis library identified the full length D-AKAP2. It is composed of 372 amino acids which includes the R binding fragment, residues 333-372, at its C-terminus. Based on coprecipitation assays, the R binding domain interacts with the N-terminal dimerization domain of RIalpha and RIIalpha. A putative RGS domain was identified near the N-terminal region of D-AKAP2. The presence of this domain raises the intriguing possibility that D-AKAP2 may interact with a Galpha protein thus providing a link between the signaling machinery at the plasma membrane and the downstream kinase.
Mesh Terms:
A Kinase Anchor Proteins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Carrier Proteins, Cloning, Molecular, Conserved Sequence, Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Cyclic AMP-Dependent Protein Kinase Type II, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, Embryo, Mammalian, GTPase-Activating Proteins, Gene Library, Macromolecular Substances, Male, Mice, Molecular Sequence Data, Organ Specificity, Proteins, RNA, Messenger, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Testis, Transcription, Genetic
A Kinase Anchor Proteins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Carrier Proteins, Cloning, Molecular, Conserved Sequence, Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Cyclic AMP-Dependent Protein Kinase Type II, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, Embryo, Mammalian, GTPase-Activating Proteins, Gene Library, Macromolecular Substances, Male, Mice, Molecular Sequence Data, Organ Specificity, Proteins, RNA, Messenger, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Testis, Transcription, Genetic
Proc. Natl. Acad. Sci. U.S.A.
Date: Oct. 14, 1997
PubMed ID: 9326583
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