Integrating positional information at the level of Smad1/5/8.

The intensity of the BMP signal is determined by cell surface receptors that phosphorylate Smad1/5/8 at the C-terminus. In addition to this BMP-activated phosphorylation, recent studies have shown that sequential phosphorylations by MAPK and GSK3 kinases can negatively regulate the activity of the pSmad1Cter signal. These phosphorylations in the linker region cause Smad1 to be transported to the centrosomal region, polyubiquitinylated and degraded by the proteasomal machinery. In Xenopus embryos, Wnt signals, which regulate GSK3, induce ectoderm to adopt an epidermal fate, and this Wnt effect requires an active BMP-Smad1/5/8 signaling pathway. These findings have profound implications for understanding how dorsal-ventral and anterior-posterior patterning are seamlessly integrated in the early embryonic morphogenetic field.