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 transcripti onal, metabolic, and developmental regulation in response to stress. In Sac charomyces cerevisiae, Snf1 is required for the response to glucose limitat ion. Snf1 kinase complexes contain the alpha (catalytic) subunit Snf1, one of the three related beta subunits Gal83, Sip1, or Sip2 and the gamma subun it Snf4. We present evidence that the beta subunits regulate the subcellula r localization of the Snf1 kinase. Green fluorescent protein fusions to Gal 83, Sip1, and Sip2 show different patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that Gal83 directs Snf1 to the nucleus i n a glucose-regulated manner. We further identify a novel signaling pathway that controls this nuclear localization in response to glucose phosphoryla tion. This pathway is distinct from the glucose signaling pathway that inhi bits Snf1 kinase activity and responds not only to glucose but also to gala ctose and sucrose. Such independent regulation of the localization and the activity of the Snf1 kinase, combined with the distinct localization of kin ases containing different beta subunits, affords versatility in regulating physiological responses.