Molecular cloning of a cdna encoding a novel human protein with a d-akap2 sequence at its carboxyl terminal domain

A kinase anchoring proteins (AKAPs) comprise a family of proteins whose name is derived from their ability to bind to regulatory subunits of protein ki nase A (PKA) and, thereby localize the kinase to specific intracellular locations. Such cornpartmentalization of PKA via AKAPs can provide specificity to and augment cAMP mediated hormone responses in cells. More recent evidente has shown that AKAPs can function as adaptor proteins promoting assembly of multiprotein signaling complexes. Here we report the molecular cloning of a human cDNA encoding a 662 amino acid protein with a D-AKAP2 domain at its carboxyl terminal region. RT PCR results showed that transcripts en coding this D-AKAP2-like protein are expressed in a variety of human tissues including brain, liver, kidney, heart, pancreas, placenta and skeletal muscle. Mouse D AKAP2, and AKAP recently isolated by yeast two hybrid screening that binds both types of regulatory subunits of PKA, is a 372 amino acid protein that contains a putative RGS domain. Amino acid residues 291-662 of the human D-AKAP2-like protein exhibit 94% identity to the mouse D-AKAP2 protein. The unique amino terminal sequence of 290 amino acids of this novel human protein exhibits no similarity to anv known proteins. The presence of this unique amino terminal domain in the context of a carboxyl terminal D-AKAP2 domain that possesses a putative RGS domain sequence raises interesting questions regarding the functional role of this protein in assembling protein complexes and in cAMP signaling (NIH Hï,41071, DK25295).