Intracellular signaling: Fleshing out the TGFβ pathway

Members of the transforming growth factor β (TGFβ) family of signalling molecules are found in a wide variety of, and perhaps all, multicellular animals and are involved in many essential developmental processes. Not surprisingly, some member of the superfamily has been found to be present in most tissues that have been examined. In the last few years, most of the effort in the study of how TGFβ ligands function has been devoted to tracing the signaling pathway from the plasma membrane to the nucleus. This bore fruit with the important discovery of the ‘Smads’, intracellular proteins that interact with, and become phosphorylated, by TGFβ receptors, and then translocate to the nucleus. Once in the nucleus, some Smads bind DNA, interact with other transcription factors and activate target genes. These studies on Smads have given us a rudimentary understanding of the signaling pathway from the ligand to the nucleus [1–3].