The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae.
Macroautophagy (hereafter autophagy) is a conserved membrane trafficking pathway responsible for the turnover of cytosolic protein and organelles during periods of nutrient deprivation. This pathway is also linked to a number of processes important for human health, including tumor suppression, innate immunity and the clearance of protein aggregates. As a result, there is tremendous interest in autophagy as a potential point of therapeutic intervention in a variety of pathological states. To achieve this goal, it is imperative that we develop a thorough understanding of the normal regulation of this process in eukaryotic cells. The Tor protein kinases clearly constitute a key element of this control as Tor activity inhibits this degradative process in all organisms examined, from yeast to man. Here, we discuss recent work indicating that the cAMP-dependent protein kinase (PKA) also plays a critical role in controlling autophagy in the budding yeast, Saccharomyces cerevisiae. A model describing how PKA activity might influence this degradative process, and how this control might be integrated with that of the Tor pathway, is presented.
Stephan
Joseph S
JS
Department of Molecular Genetics and Program in Molecular, Cellular and Developmental Biology, The Ohio State University, Columbus, OH, USA.
Yeh
Yuh-Ying
YY
Ramachandran
Vidhya
V
Deminoff
Stephen J
SJ
Herman
Paul K
PK
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
C413216:ATG13 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; D017868:Cyclic AMP-Dependent Protein Kinases