title: Modulation of the Bioactive Conformation of Transforming Growth Factor β: Possible Implications of Cation Binding for Biological Function.
abstract: In any organism, very precisely adjusted interaction and exchange of information between cellsis continuously required. These cooperative interactions involve numerous cytokines, acting throughcorresponding sets of cell-surface receptors. The transforming growth factor β (TGF-β)superfamily includes a variety of structurally related multifunctional cytokines that play criticalroles in maintaining cellular homeostasis and controlling cell fate. Response of a cell to a specificsignal it receives should depend upon the current state of the environment, including concentrationsof biologically relevant ions. One of the most biologically active ions, calcium, acts upon a specificcalcium signaling system that operates over a wide temporal range and regulates many cellularprocesses in continuous "cross-talk" with the TGF-β signaling system. In additionto that, the structural and dynamical properties of TGF-β molecules, along with detected directinteraction of them with the biologically relevant cations suggest another level of fine regulationof TGF-β activity. The fact that both mono- and divalent cations bind in the same low-affinitysites implies that some competition of cations for interaction with TGF-β can also occur in vivo,contributing to the diversity of TGF-β biological functions.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, ul. Miklukho-Maklaya, 16/10, 117997, Moscow, Russia, bon@nmr.ru.
authors.forename: Eduard V
authors.initials: EV
authors.lastname: Bocharov
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Pavlov
authors.forename: Marcel J J
authors.initials: MJ
authors.lastname: Blommers
authors.forename: Tudor
authors.initials: T
authors.lastname: Arvinte
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev