Subcellular localization of the Snf1 kinase is regulated by specific beta subunits and a novel glucose signaling mechanism.
The Snf1/AMP-activated protein kinase family has broad roles in transcriptional, metabolic, and developmental regulation in response to stress. In Saccharomyces cerevisiae, Snf1 is required for the response to glucose limitation. Snf1 kinase complexes contain the alpha (catalytic) subunit Snf1, one of the three related beta subunits Gal83, Sip1, or Sip2, and the gamma subunit Snf4. We present evidence that the beta subunits regulate the subcellular localization of the Snf1 kinase. Green fluorescent protein fusions to Gal83, Sip1, and Sip2 show different patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that Gal83 directs Snf1 to the nucleus in a glucose-regulated manner. We further identify a novel signaling pathway that controls this nuclear localization in response to glucose phosphorylation. This pathway is distinct from the glucose signaling pathway that inhibits Snf1 kinase activity and responds not only to glucose but also to galactose and sucrose. Such independent regulation of the localization and the activity of the Snf1 kinase, combined with the distinct localization of kinases containing different beta subunits, affords versatility in regulating physiological responses.
Vincent
O
O
Departments of Genetics and Development and Microbiology, Molecular Biology and Biophysical Studies, Columbia University, New York, New York 10032, USA.
Townley
R
R
Kuchin
S
S
Carlson
M
M
D055372:AMP-Activated Protein Kinases; D002244:Carbon / Q000378:metabolism; D002352:Carrier Proteins; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D005285:Fermentation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013347:Subcellular Fractions; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D005656:Fungal Proteins; C085569:GAL83 protein, S cerevisiae; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C091267:SIP2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D002244:Carbon; D011494:Protein Kinases; C071570:SNF1-related protein kinases; D006593:Hexokinase; D017346:Protein Serine-Threonine Kinases; C075934:SIP1 protein, S cerevisiae; C078651:SNF4 protein, S cerevisiae; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D005690:Galactose