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 developmen t, erythropoiesis and the local regulation of many tissues. At the post-tra nslational level, the amount of activin A produced by cells may be modulate d 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 fol listatin and alpha(2)-macroglobulin, that have consequences for receptor av ailability. In common with other TGF beta family members, activin signals t hrough pairs of type I and II receptor kinases and the Smad intracellular s ignalling cascade. Other checkpoints have been identified such as the recen tly identified pseudo-receptor, BAMBI. These emerging findings point to a t ightly coordinated regulation of the exposure of a cell or tissue to activi n, consistent with the low amounts of this potent factor that are necessary to modulate cellular responses. (C) 2000 John Wiley & Sons, Inc.