Residues in the C-terminal region of activin A determine specificity for follistatin and type II receptor binding.
Activin is a secreted growth factor that signals by binding two related classes of single transmembrane receptors at the cell surface. The interaction of activin with its receptors is highly regulated by other cell surface receptors, antagonistic ligands, and high affinity extracellular binding proteins such as follistatin. Two activin A mutants, the deletion mutant des[85-109]-activin A and the point mutant K102E-activin A (K102E), were investigated with respect to their ability to bind cell surface receptors and the binding protein follistatin. The deletion mutant exhibits low affinity for both receptors and follistatin whereas the point mutant fails to bind cell surface receptors but binds follistatin-288 with high affinity. K102E is able to compete with wild type activin to bind to follistatin and can thus increase the concentration of activin available for receptor binding and signaling. These findings underline the importance of the C-terminal region of activin for binding interactions and show that different residues in this region are involved in cell surface receptor and follistatin interactions.
Fischer
W H
WH
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 N Torrey Pines Road, La Jolla, California 92037, USA. fischer@salk.edu
Park
M
M
Donaldson
C
C
Wiater
E
E
Vaughan
J
J
Bilezikjian
L M
LM
Vale
W
W
D028341:Activins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D002460:Cell Line; D002478:Cells, Cultured; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D038681:Follistatin / Q000378:metabolism*; D017353:Gene Deletion; D028322:Inhibin-beta Subunits / Q000235:genetics* / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism
D038681:Follistatin; D011956:Receptors, Cell Surface; C422405:activin A; D028341:Activins; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits; D008156:Luciferases