title: Multiplicity of the beta form of the cAMP-dependent protein kinase inhibitor protein generated by post-translational modification and alternate translational initiation.
abstract: Two distinct species of the thermostable inhibitor of the cAMP-dependent protein kinase, PKIalpha and PKIbeta, exist that are the products of separate genes. The PKIbeta form, as first isolated from rat testis, is a 70-amino acid protein, but the genomic sequence suggested that an alternate form might exist, arising as a consequence of alternate translational initiation. This species, now termed PKIbeta-78, has been synthesized by bacterial expression, demonstrated to be equipotent with PKIbeta-70, and also now demonstrated to occur in vivo. By Western blot analyses, six additional species of PKIbeta are also evident in tissues. Two of these represent the phospho forms of PKIbeta-78 and PKIbeta-70. The other four represent phospho and dephospho forms of two higher molecular mass PKIbeta species. These latter forms are currently termed PKIbeta-X and PKIbeta-Y, awaiting the full elucidation of their molecular identity. In adult rat testis and cerebellum, PKIbeta-70, PKIbeta-X, and PKIbeta-Y constitute 39, 23, and 32% and 15, 29, and 54% of the total tissue levels, respectively. In adult rat testis, 35-42% of each of these three species is present as a monophospho form, whereas no phosphorylation of them is evident in cerebellum. PKIbeta-78 is present at much lower levels in both rat testis and cerebellum (approximately 6 and 2% of the total, respectively) and almost entirely as a monophospho species. PKIbeta-78, like PKIbeta-70, is a high affinity and specific inhibitor of the cAMP-dependent protein kinase. PKIbeta-Y and PKIbeta-X, in contrast, also significantly inhibit the cGMP-dependent protein kinase.
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Davis, California 95616, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.forename: S M
authors.initials: SM
authors.lastname: Van Patten
authors.forename: D A
authors.initials: DA
authors.lastname: Walsh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D051381:Rats; D009626:Terminology as Topic; D013737:Testis / Q000737:chemistry
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C498433:Pkib protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases