Regulation of activin's access to the cell: why is Mother Nature such a control freak?

Activin A is a pluripotent growth factor with important roles in development, erythropoiesis and the local regulation of many tissues. At the post-translational level, the amount of activin A produced by cells may be modulated through the diversion of activin A subunits into the formation of inhibin or other activins containing heterodimeric forms. Once assembled, activin interacts with various low- and high-affinity binding proteins, such as follistatin and alpha(2)-macroglobulin, that have consequences for receptor availability. In common with other TGFbeta family members, activin signals through pairs of type I and II receptor kinases and the Smad intracellular signalling cascade. Other checkpoints have been identified such as the recently identified pseudoreceptor, BAMBI. These emerging findings point to a tightly coordinated regulation of the exposure of a cell or tissue to activin, consistent with the low amounts of this potent factor that are necessary to modulate cellular responses.