A novel role for yeast casein kinases in glucose sensing and signaling

Yeasts have sophisticated signaling pathways for sensing glucose, their preferred carbon source, to regulate its uptake and metabolism. One of these is the sensor/receptor-repressor (SRR) pathway, which detects extracellular glucose and transmits an intracellular signal that induces expression of HXT genes. The yeast casein kinases (Ycks) are key players in this pathway. Our model of the SRR pathway had the Ycks functioning downstream of the glucose sensors, transmitting the signal from the sensors to the Mth1 and Std1 corepressors that are required for repression of HXT gene expression. However, we found that overexpression of Yck1 fails to restore glucose signaling in a glucose sensor mutant. Conversely, overexpression of a glucose sensor suppresses the signaling defect of a yck mutant. These results suggest that the Ycks act upstream or at the level of the glucose sensors. Indeed, we found that the glucose sensor Rgt2 is phosphorylated on Yck consensus sites in its C-terminal tail in a Yck-dependent manner and that this phosphorylation is required for corepressor binding and ultimately HXT expression. This leads to a revised model of the SRR pathway in which the Ycks prime a site on the cytoplasmic tails of the glucose sensors to promote binding of the corepressors.