Gcn2 mediates Gcn4 activation in response to glucose stimulation or UV radiation not via GCN4 translation

In mammalian cells transcription factors of the AP-1 family are activated b y either stress signals such as W radiation, or mitogenic signals such as g rowth factors. Here we show that a similar situation exists in the yeast Sa ccharomyces cerevisiae, The AP-1 transcriptional activator Gcn4, known to b e activated by stress signals such as UV radiation and amino acids starvati on, is also induced by growth stimulation such as glucose. We show that glu cose-dependent Gcn4 activation is mediated through the Ras/cAMP pathway. Th is pathway is also responsible for UV-dependent Gcn4 activation but is not involved in Gcn4 activation by amino acid starvation. Thus, the unusual phe nomenon of activation of mitogenic pathways and AP-1 factors by contradicto ry stimuli through Has is conserved from yeast to mammals. We also show tha t activation of Gcn4 by glucose and W requires Gcn2 activity. However, in c ontrast to its role in amino acid starvation, Gcn2 does not increase eIF2 a lpha phosphorylation or translation of GCN4 mRNA in response to glucose or UV. These findings suggest a novel mechanism of action for Gcn2, The findin g that Gcn4 is activated in response to glucose via the Ras/cAMP pathway su ggests that this cascade coordinates glucose metabolism with amino acids an d purine biosynthesis and thereby ensures availability of both energy and e ssential building blocks for continuation of the cell cycle.