Molecular Cloning of a Tissue-Specific Protein Kinase (Cγ) from Human Testis—Representing a Third Isoform for the Catalytic Subunit of cAMP-Dependent Protein Kinase

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Abstract
Two different mammalian genes for the catalytic subunit (C) of cAMP-dependent protein kinase have previously been characterized (C.alpha., C.beta.). In the present study, we report the molecular cloning of a third isoform of C, from a human testis cDNA library, as well as the isolation of human cDNAs for C.alpha. and C.beta.. This third form of C, which we will designate C.gamma., is clearly derived from a distinct gene and shows a tissue-specific expression. A close evolutionary relation between C.gamma. and C.alpha. was suggested by nucleotide homologies (86% inside the open reading frame, 81% in the 3''-untranslated region). Thus, the C.gamma. cDNA cross-hybridized with the 2.8 kilobase (kb) c.alpha. mRNA, present at high levels in most human tissues, as well as with a 1.8 kg C.gamma.-specific mRNA, which was only found at detectable levels in human testis. However, at the amino acid level, C.alpha. and C.beta. showed a close relationship (93% homology), whereas C.gamma. diverged significantly from both C.alpha. (83%) and C.beta. (79%). Taken together with the tissue-specific expression of C.gamma., this suggests a pressure on C.gamma. during evolution, acting to modulate it in a functionally specific way. Certain amino acid substitutions make C.gamma. a distinct member of the cAMP-dependent subfamily of protein kinases, and suggest that C.gamma. may be distinct in its protein substrate specificity or its interaction with the different regulatory subunits.