Characterization of the Human Gene Encoding the Type Iα and Type Iβ cGMP-Dependent Protein Kinase (PRKG1)

Abstract

The type I cGMP-dependent protein kinase (cGK) has been shown to play a crucial role in the relaxation of vascular smooth muscle by lowering the intracellular level of calcium. Two isoforms of type I cGK have been described, type Iα and type Iβ, differing only in their N-terminal parts. This report describes the cloning of the gene PRKG1 encoding both human type I cGK isoforms. PRKG1 is a single-copy gene consisting of 19 exons encompassing at least 220 kb. Several of the splice sites previously observed in theDrosophila melanogasterDG2 gene have been conserved in PRKG1, and these conserved splice sites correlated well with the boundaries between several of the previously proposed functional domains of type I cGK. The first two exons of the type I cGK gene were shown to encode the type Iα- and type Iβ-specific parts of the cGK. Using 5′-rapid amplification of cDNA ends, potential sites for transcription initiation were identified 5′ upstream of both these exons. Northern blot analyses demonstrated distinct patterns of expression of the isoforms of type Iα and Iβ cGK in different human tissues.