Components of the mitogen-activated protein kinase (MAPK) pathway for cell signaling in yeast are reused in related pathways that produce very different biological outcomes. So how does a cell know, for example, whether it should grow or mate? Enter Ste5, the prototypical scaffold protein, which binds the set of components from the mating pathway, presumably to sequester them so they can be activated specifically. But Zalatan et al. (see the Perspective by Davis) found something rather different. Ste5 is not just an inert support structure; it apparently has an active role in the regulatory pathway as an allosteric inhibitor of the MAPK Fus3. It only unclamps Fus3 function when a signal unique to the mating pathway brings Ste5 to the cell membrane.
J. G. Zalatan, S. M. Coyle, S. Rajan, S. S. Sidhu, W. A. Lim, Conformational control of the Ste5 scaffold protein insulates against MAP kinase misactivation. Science 337, 1218–1222 (2012). [Abstract] [Full Text]