+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Functional analysis of mutations in the gamma 2 subunit of AMP-activated protein kinase associated with cardiac hypertrophy and Wolff-Parkinson-White syndrome.

      The Journal of Biological Chemistry
      AMP-Activated Protein Kinases, Amino Acid Sequence, Amino Acid Substitution, Cardiomegaly, enzymology, genetics, Carrier Proteins, Humans, Kinetics, Molecular Sequence Data, Multienzyme Complexes, chemistry, metabolism, Mutagenesis, Mutagenesis, Site-Directed, Mutation, Phosphorylation, Protein Kinases, Protein Subunits, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Stress, Mechanical, Transcription Factors, Wolff-Parkinson-White Syndrome

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Mutations in the gene encoding the gamma(2) subunit of the AMP-activated protein kinase (AMPK) have recently been shown to cause cardiac hypertrophy and ventricular pre-excitation (Wolff-Parkinson-White syndrome). We have examined the effect of four of these mutations on AMPK activity. The mutant gamma(2) polypeptides are all able to form functional complexes following co-expression with either alpha(1)beta(1) or alpha(2)beta(1) in mammalian cells. None of the mutations caused any detectable change in the phosphorylation of threonine 172 within the alpha subunit of AMPK. Consequently, in the absence of an appropriate stimulus the mutant complexes, like the wild-type complex, exist in an inactive form demonstrating that the mutations do not lead to constitutive activation of the kinase. Three of the mutations we studied occur within the cystathionine beta-synthase (CBS) domains of gamma(2). Two of these mutations lead to a marked decrease in AMP dependence, whereas the third reduces AMP sensitivity. These findings suggest that the CBS domains play an important role in AMP-binding within the complex. In contrast, a fourth mutation, which lies between adjacent CBS domains, has no significant effect on AMPK activity in vitro. These results indicate that mutations in gamma(2) have different effects on AMPK function, suggesting that they may lead to abnormal development of the heart through distinct mechanisms.

          Related collections

          Author and article information


          Comment on this article