Cross-talk between the bone morphogenetic protein pathway and other major signaling pathways results in tightly...

Members of the bone morphogenetic protein (BMP) family of ligands have been identified in a variety of vertebrate and invertebrate species and have been shown to play an essential role in a range of biological processes, including mesodermal patterning and organ development, as well as the formation of bone and cartilage. Although the interaction of BMP ligands with specific type I and II serine-threonine kinase receptor complexes is crucial to the initiation of signaling, it is the interaction of intracellular signaling molecules, called Smads, with receptor complexes and other transcription factors that defines the repertoire of biological responses associated with the BMPs. But although all BMP ligands appear to interact with specific type I and II receptors, growing biochemical and developmental evidence supports the notion that alternative non-Smad pathways also participates in BMP signaling. Here, we review the interaction or 'cross-talk' between the BMP and other major signaling pathways (transforming growth factor beta/activin, Notch, p38 mitogen-activated protein kinase and Toll) that results in tightly regulated cell-specific outcomes.