Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway byprotein interactions

TheRas/Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracell ular-signal-regulated kinase) pathway is at the heart of signalling network s that govern proliferation, differentiation and cell survival. Although th e basic regulatory steps have been elucidated, many features of this pathwa y are only beginning to emerge. This review focuses on the role of protein- protein interactions in the regulation of this pathway, and how they contri bute to co-ordinate activation steps, subcellular redistribution, substrate phosphorylation and cross-talk with other signalling pathways.