Editors' ChoiceMAPK Signaling

Specificity Through Degradation

Science's STKE  04 Jan 2005:
Vol. 2005, Issue 265, pp. tw3
DOI: 10.1126/stke.2652005tw3

Yeasts use partially overlapping kinase modules to specify discrete cellular responses. For example, the upstream kinases in the mitogen-activated protein kinase (MAPK) cascade Ste11 and Ste7 are both activated during mating response signaling and during filamentous growth signaling. The MAPK Kss1 then triggers the filamentous growth transcriptional cascade and the MAPK Fus3 triggers the mating response genes. In the absence of Fus3, pheromone signaling stimulates Kss1 and filamentous growth gene expression, which suggests that Fus3 has a role in suppressing filamentous growth responses during pheromone signaling. Two groups (Chou et al. and Bao et al.) report that Fus3 triggers the degradation of a transcription factor required for filamentous growth, Tec1, to maintain signaling specificity through the shared MAPK pathways. Both groups found that the abundance of Tec1 decreased after mating stimulated by pheromone and that this destabilization required Fus3, but not Kss1. Both groups identified Tec1 Thr273 as the residue phosphorylated by Fus3. Degradation was mediated by an SCF ubiquitin ligase complex; however, Chou et al. reported the requirement for the Cdc4 subunit and Bao et al. reported that the Dia2 subunit was necessary. Despite this difference in the reported composition of the SCF complex, the results from both groups indicate that selective degradation of a transcriptional regulator is one mechanism by which signaling specificity is achieved.

S. Chou, L. Huang, H. Liu, Fus3-regulated Tec1 degradation through SCFCdc4 determines MAPK signaling specificity during mating yeast. Cell 119, 981-990 (2004). [PubMed]

M. Z. Bao, M. A. Schwartz, G. T. Cantin, J. R. Yates III, H. D. Madhani, Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast. Cell 119, 991-1000 (2004). [PubMed]