Stopping smad

Elusive smad dephosphorylase identified

In the March 15th issue of G&D, Dr. Lan Xu and colleagues (UMASS Medical School) identify the long sought-after phosphatase for Smad in the BMP signal transduction pathway.

In organisms as diverse as worms, fruit flies and humans, the Smad family of intracellular messenger proteins are activated upon phosphorylation by TGFbeta and BMP signaling pathways. Dr. Xu’s new paper now reveals the elusive Smad phosphatase in the BMP pathway. The researchers used an RNAi approach to identify pyruvate dehydrogenase phosphatase (PDP) as being required for the dephosphorylation – and thus inactivation – of MAD, a Drosophila Smad protein.

The authors also demonstrated that mammalian PDPs are involved in the dephosphorylation of BMP-activated Smad1, but not TGFbeta-activated Smad2 or Smad3. Dr. Xu emphasizes that, “we are excited now that we have a new entry point to the bigger question of how BMP signals can be downregulated in various physiological contexts”.