Signaling inputs converge on nuclear effecters in TGF-beta signaling

Recent studies have consolidated the pivotal role of Smads as intracellular effecters of TGF-beta family members. Upon binding to their specific type I and type II serine/threonine kinase receptors, each family member activat es a particular subset of Smad proteins. Activated, receptor-regulated Smad s form hetero-oligomeric complexes with common-partner Smads that transloca te into the nucleus, where they control the expression of target genes in a cell-type-specific manner. Smads appear to function not only as nuclear ef fecters for TGF-beta family members, but as signal integrators within an ex tensive intracellular network.