<p>Transforming growth factor beta (TGF-beta) is a member of a large family ofsecreted growth factors of central importance in eukaryotic development andhomeostasis. Members of this family, which includes the activins, inhibins andbone morphogenic proteins (BMPs), bind to receptors that consist of twotransmembrane serine/threonine (Ser/Thr) kinases called the type I and type IIreceptors. Type II activates Type Iupon formation of the ligand receptor complex by multiply phosphorylating theGS domain, a short (~30 residues), highly conserved regulatory sequence justN-terminal to the kinase domain on the cytoplasmic side of the receptor. TheGS domain is found only in the type I receptor family and is named for theTTSGSGSG sequence at its core. At least three, and perhaps four to five of theserines and threonines in the GS domain, must be phosphorylated to fullyactivate TbetaR-1 [<cite idref="PUB00021804"/>].</p><p>The GS domain forms a helix-loop-helix structure in which the sites ofactivating phosphorylation are situated in a loop known as the GS loop. One key role for phosphorylation is to block the adoption of aninactivating configuration by the GS domain [<cite idref="PUB00023523"/>].</p>