TGFβ is part of a large family of structurally related secreted signaling proteins, which also includes activ-ins and bone morphogenetic proteins (BMPs). that have an important role in intracellular communication during development and tissue homeostasis. TGFβ regulates the proliferation, differentiation, migration, and apoptosis of many different cell types through interaction with different receptor types: TGF0 type I receptor (TβR-I) and TGFβ type II receptor (TβR-II) are required for TGFβ signal transduction, whereas TGFβ type III receptor (ТβR-III) and endoglin appear to have a more indirect role in signal transduction, and may act asaccessory receptors. TβR-I and TβR-II were found to encode serine/ threonine kinases. TGFβ-mediated receptor activation involves formation of heteromeric oligomers of two distinct sequentially acting kinases; the constitu-tively active TβR-II kinase phosphorylates and activates TβR-I. Recently, genetic studies in Drosophila and Caenorhabditis elegans have led to the identification of downstream effector molecules of the TGFβ receptor complex, known as Smad proteins. Smads relay the signal from the membrane to the nucleus; Smad2 and Smad3 transiently interact with and become phosphorylated by the activated TβR-I, and form heteromeric complexes with Smad4 that translocate to the nucleus, where they act as transcriptional regulators of target genes.

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