title: Unchaining the beast; insights from structural and evolutionary studies on TGFβ secretion, sequestration, and activation.
abstract: TGFβ is secreted in a latent state and must be "activated" by molecules that facilitate its release from a latent complex and allow binding to high affinity cell surface receptors. Numerous molecules have been implicated as potential mediators of this activation process, but only a limited number of these activators have been demonstrated to play a role in TGFβ mobilisation in vivo. Here we review the process of TGFβ secretion and activation using evolutionary data, sequence conservation and structural information to examine the molecular mechanisms by which TGFβ is secreted, sequestered and released. This allows the separation of more ancient TGFβ activators from those factors that emerged more recently, and helps to define a potential hierarchy of activation mechanisms.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, 550 First Avenue, Cell Biology Floor 6 Room 650, Medical Science Building, New York, NY 10016, United States. Electronic address: ian.butler.robertson@gmail.com.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Robertson
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Rifkin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D017510:Protein Folding; D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta
keywords: Activation; Evolution; Extracellular matrix; LTBP; TGFβ