Activin isoforms signal through type I receptor serine/threonine kinase ALK7.
Activins play a fundamental role in cell differentiation and development. Activin A signaling is mediated through a combination of activin type II receptors (ActRIIs) and the activin type IB receptor, ALK4. Signaling receptors of other activin isoforms remain to be elucidated. Here, we found that activin AB and activin B are ligands for ALK7. ALK7 is an orphan receptor serine/threonine kinase expressed in neuroendocrine tissues including pancreatic islets. The combination of ActRIIA and ALK7, preferred by activin AB and activin B but not by activin A, is responsible for activin-mediated secretion of insulin from pancreatic beta cell line, MIN6. In contrast, all activins activate a combination of ActRIIA and ALK4 with various levels of potency. Thus, variation in activin signaling through type I receptors is dependent upon homo- and heterodimeric assembly of activin isoforms. Thus, the differential combination of receptor heterodimers mediates variation in activin isoform signaling.
Tsuchida
Kunihiro
K
Institute for Enzyme Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. tsuchida@ier.tokushima-u.ac.jp
Nakatani
Masashi
M
Yamakawa
Norio
N
Hashimoto
Osamu
O
Hasegawa
Yoshihisa
Y
Sugino
Hiromu
H
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D028341:Activins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D028322:Inhibin-beta Subunits / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012995:Solubility
C422403:INHBA protein, Bos taurus; C422402:INHBB protein, human; C498905:Inhbb protein, mouse; D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; C044147:activin B; D028341:Activins; D028322:Inhibin-beta Subunits; C424205:ACVR1C protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A