Modulation of the Bioactive Conformation of Transforming Growth Factor β: Possible Implications of Cation Binding for Biological Function.

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.