Sustained specificity

Many cell signaling circuits are not well insulated from one another: there are too many signals and too few signaling components for that. Now, researchers have found that mating and invasive-growth pathways in budding yeast may be differentiated by the extent of activation of the same components. The two yeast pathways use the same upstream kinases to activate the two MAP kinases, Fus3 and Kss1. Thanks to a pathway-specific scaffolding protein, Fus3 was thought to be specific to the mating pathway, and Kss1 to the invasive-growth pathway. Fus3 was proposed to act as a specificity factor by sterically preventing the association of Kss1 with the mating-specific scaffolding protein.

Now, Lee Bardwell and colleagues of the University of California, Irvine, CA, report that Kss1 is activated during mating, although the period of activation is shorter than for Fus3. This limitation on Kss1 is dependent not only on the presence of Fus3 but also (contrary to previous results) on Fus3 activity. The relevant target of Fus3 has not yet been determined.

“The idea that the specificity involves transient versus sustained activation of MAP kinase opens up a whole series of parallels with mammalian systems,” says Bardwell. In rat neurons, for example, transient MAP kinase activation downstream of EGF results in proliferation, whereas sustained activation downstream of NGF results in differentiation.The method by which sustained activation is decoded is unknown. One possibility is that a kinase must be active for long enough both to induce transcription and to phosphorylate the product of that transcription. ▪

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