Figure 15.

TGFβ signaling family. The TGFβ signaling family regulates cell proliferation and differentiation in diverse biological processes including reproduction, cancer progression, extracellular matrix formation, inflammation, metabolism, and development of bone, skeletal muscle, and fat. The family consists of extracellular antagonists that bind TGFβ ligands and modulate their biological availability. The receptors in this family are serine/threonine kinases. Ligands bind to type II receptors, which then recruit and phosphorylate the type I receptor, initiating signaling through phosphorylation of intracellular Smads. Fibrillins and follistatin are extracellular antagonists of ligands in the TGFβ signaling family. A variant within an intron in the fibrillin-3 gene has been linked and associated with PCOS. The follistatin gene has been linked with PCOS in an affected sib pair study. The fibrillin-3 variant is also associated with a metabolic phenotype in women with PCOS and their brothers. These observations suggest that genes in the TGFβ signaling family are candidate genes for PCOS.