title: A mutation in the catalytic subunit of cAMP-dependent protein kinase that disrupts regulation.
abstract: A mutant catalytic subunit of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase has been isolated from Saccharomyces cerevisiae that is no longer subject to regulation yet retains its catalytic activity. Biochemical analysis of the mutant subunit indicates a 100-fold decreased affinity for the regulatory subunit. The mutant catalytic subunit exhibits approximately a threefold increase in Michaelis constant for adenosine triphosphate and peptide cosubstrates, and is essentially unchanged in its catalytic rate. The nucleotide sequence of the mutant gene contains a single nucleotide change resulting in a threonine-to-alanine substitution at amino acid 241. This residue is conserved in other serine-threonine protein kinases. These results identify this threonine as an important contact between catalytic and regulatory subunits but only a minor contact in substrate recognition.
authors.affiliation: Cold Spring Harbor Laboratory, NY 11724.
authors.forename: L R
authors.initials: LR
authors.lastname: Levin
authors.forename: J
authors.initials: J
authors.lastname: Kuret
authors.forename: K E
authors.initials: KE
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Powers
authors.forename: S
authors.initials: S
authors.lastname: Cameron
authors.forename: T
authors.initials: T
authors.lastname: Michaeli
authors.forename: M
authors.initials: M
authors.lastname: Wigler
authors.forename: M J
authors.initials: MJ
authors.lastname: Zoller
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D000242:Cyclic AMP / Q000494:pharmacology*; D005800:Genes, Fungal; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D013329:Structure-Activity Relationship; D013912:Threonine
chemical_list: D046911:Macromolecular Substances; D013912:Threonine; D000242:Cyclic AMP; D011494:Protein Kinases