Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability to respond to available nutrients is critical for all living cells. The AMP-activated protein kinase (SNF1 in yeast) is a central regulator of metabolism that is activated when energy is depleted. We found that SNF1 activity in the nucleus is regulated by controlled relocalization of the SNF1 activator Std1 into puncta. This process is regulated by glucose through the activity of the previously uncharacterized protein kinase Vhs1 and its substrate Sip5, a protein of hitherto unknown function. Phosphorylation of Sip5 prevents its association with Std1 and triggers Std1 accretion. Reversible Std1 puncta formation occurs under non-stressful, ambient conditions, creating non-amyloid inclusion bodies at the nuclear-vacuolar junction, and it utilizes cellular chaperones similarly to the aggregation of toxic or misfolded proteins such as those associated with Parkinson's, Alzheimer's, and CJD diseases. Our results reveal a controlled, non-pathological, physiological role of protein aggregation in the regulation of a major metabolic cellular pathway.
 ...
PMID:The Std1 Activator of the Snf1/AMPK Kinase Controls Glucose Response in Yeast by a Regulated Protein Aggregation. 2927 1

Glucose is the preferred carbon of the yeast Saccharomyces cerevisiae. Depletion of glucose activates SNF1 (yeast AMP-activated protein kinase-AMPK), allowing cells to switch from fermentation to respiration. We have recently characterized the mechanism by which SNF1 activity is regulated by the Std1 protein, and its regulator Sip5. The hitherto uncharacterized protein kinase Vhs1 phosphorylates Sip5 in response to glucose availability, disengaging it from Std1 and promoting the sequestering of the SNF1 activator out of the nucleus into cytoplasmic puncta. These aggregates, which have the properties of liquid drops, and not of amyloids, reside in the nucleus-vacuole junction. The process is reversible, and Std1 puncta dissolve when glucose becomes scarce again. This reversible process requires protein chaperones, similar to the aggregation of toxic or misfolded proteins such as those associated with Huntington's Chorea, Alzheimer's and CJD diseases. Our results thus reveal a regulated, non-pathological, physiological role of protein aggregation that controls a major metabolic cellular pathway.
 ...
PMID:A reversible liquid drop aggregation controls glucose response in yeast. 2932 48