Scaffolding proteins: not such innocent bystanders

Abstract

Sequential transfer of information from one enzyme to the next within the confines of a protein kinase scaffold enhances signal transduction. Though frequently considered to be inert organizational elements, two recent reports implicate kinase-scaffolding proteins as active participants in signal relay.

Figure 1. Scaffolding proteins offer additional modes of regulation in signaling cascades

(A) In yeast, mitotic exit requires Nud1 phosphorylation by Cdc15. This essential step causes recruitment of the Dbf2–Mob1 kinase complex to spindle pole bodies, where it is activated by Cdc15 (adapted from [6]). (B) In mammalian cells, Cdk1–cyclinB phosphorylates the AKAP gravin during the cell cycle, and allows phosphorylation-dependent binding of Plk1. Active Plk1 recruitment in the complex is then able to locally phosphorylate targets that are crucial for cell-cycle progression. (C) A third example of phosphorylation-dependent interactions comes from scaffolding in the Wnt signaling pathway. Axin is a scaffolding protein that participates in both β-catenin ‘stabilization complexes’ and β-catenin ‘destruction’ complexes. The formation of these complexes is dependent on phosphorylation–dephosphorylation cycles that are based on the balance between GSK3β and PP1cγ (PP1) activities (adapted from [7]).