TRIP6 transcriptional co-activator is a novel substrate of AMP-activated protein kinase.
AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that acts as a sensor of cellular energy charge. Once activated it switches on catabolic pathways and switches off many ATP-consuming processes (anabolic pathways) to preserve the energy status of the cell. In order to identify new targets of AMPK action we have performed a two-hybrid screening of a human pancreas cDNA library. As a result, we have identified TRIP6 as a novel target of AMPK action. This protein belongs to the zyxin family of proteins located at the focal adhesion plaques in the plasma membrane, although they may also travel to the nucleus, where they have regulatory properties. We confirmed the physical interaction between the catalytic subunit (AMPK-alpha2) of the AMPK complex and TRIP6 in mammalian cells by two-hybrid and co-immunoprecipitation assays. We also showed that AMPK was able to phosphorylate in vitro TRIP6 at the N-terminus. Finally, we present evidence that transcriptional co-activator properties of TRIP6 were enhanced by AMPK action.
Solaz-Fuster
M Carmen
MC
Instituto de Biomedicina de Valencia CSIC, Jaime Roig 11, 46010-Valencia, Spain.
Gimeno-Alcañiz
José Vicente
JV
Casado
Marta
M
Sanz
Pascual
P
D055372:AMP-Activated Protein Kinases; D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D060588:LIM Domain Proteins; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012265:Ribonucleotides / Q000494:pharmacology; D013379:Substrate Specificity; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; D009097:Multienzyme Complexes; D016328:NF-kappa B; C092282:PSMC5 protein, human; D012265:Ribonucleotides; D015534:Trans-Activators; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; C031143:AICA ribonucleotide