Kinase cascades: modularity, localization, and signal processing behaviors

26 March 2010

Peter Pryciak
Cell Dynamics Group
University of Massachusetts Medical School


Using a model system (yeast pheromone response), we study the regulated membrane localization of signaling proteins and how localization affects signal processing through a MAP kinase cascade. Our studies indicate that the proper localization of several signaling proteins requires the concerted action of multiple weak-affinity binding motifs [1,2]. We hypothesize that the use of multiple weak interactions offers three advantages over single strong interactions: it is easier to evolve; it increases spatiotemporal dynamics; and it allows for additional regulatory input [2,3]. Membrane localization also has unexpected effects on the propagation of signal through the MAP kinase cascade [4]. For example, it can help shape the input-output properties of the pathway, such as promoting a graded (rather than switch-like) response to increasing levels of stimulus [5]. Recently, we found that membrane recruitment of a pathway scaffold protein can promote signaling in trans between kinases that are bound to separate scaffold molecules. This behavior may loosen some binding constraints expected for scaffold proteins, perhaps contributing to rapid evolution of new signaling proteins and pathways.


  1. J J Winters, R E Lamson, H Nakanishi, A M Neiman, P M and Pryciak, "A membrane binding domain in the Ste5 scaffold synergizes with Gbetagamma binding to control localization and signaling in pheromone response", Mol Cell 20:21-32. 2005. PubMed
  2. S Takahashi, P M Pryciak, "Identification of novel membrane-binding domains in multiple yeast Cdc42 effectors", Mol Biol Cell 18:4945-56 2007. PubMed
  3. S C Strickfaden, M J Winters, G Ben-Ari, R E Lamson, M Tyers, P M Pryciak, "A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway", Cell 128:519-531 2007. PubMed
  4. R E Lamson, S Takahashi, M J Winters, P M Pryciak, "Dual role for membrane localization in yeast MAP kinase cascade activation and its contribution to signaling fidelity", Curr Biol 16:618-623 2006. PubMed
  5. S Takahashi, P M Pryciak, "Membrane localization of scaffold proteins promotes graded signaling in the yeast MAP kinase cascade", Curr Biol 18:1184-1191 2008. PubMed

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