A proteomic approach has identified a new regulator in a key cell signalling pathway.

The Raf–MEK–ERK pathway is an important route by which external signals are passed to the nucleus, influencing cell growth, proliferation, migration, differentiation and survival. Raf-1 kicks off the chain of signalling. Although much is known about its activation, how it is switched off has been less clear.

Amardeep Dhillon, Walter Kolch and colleagues in Glasgow used a functional proteomics approach to monitor dynamic changes in protein interactions, in order to identify molecules that switch off Raf-1 signalling. They discovered that protein phosphatase 5 binds to Raf-1 and selectively removes an essential phosphate group, inactivating the protein and preventing signalling through the Raf–MEK–ERK pathway. They also showed that this regulation affects a cell's decision to proliferate or differentiate.

The results suggest that PP5 is a physiological regulator of Raf-1 signalling pathways, and thus an important factor in the control of cell fate decisions.

• This research was supported by the Wellcome Trust, Cancer Research UK and the European Union.

Image: Cell nucleus, courtesy of Dr David Furness.

External links

• von Kriegsheim A et al. Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5. Nat Cell Biol 2006;8(9):1011–6.