Novel activin receptors: distinct genes and alternative mRNA splicing generate a repertoire of serine/threonine kinase receptors.
We have cloned ActR-IIB, which encodes four new activin receptor isoforms belonging to the protein serine/threonine kinase receptor family. Two of the ActR-IIB isoforms have higher affinity for activin A than the previously cloned activin receptor and differ from each other by the inclusion of an alternatively spliced segment in the cytoplasmic juxtamembrane region. A second alternative splicing event generates two additional receptor isoforms that lack a proline cluster in the external juxtamembrane region and have lower affinity for activin A. All isoforms bind inhibin A with low affinity. Thus, the repertoire of activin receptors includes species that differ in ligand binding affinity, cytoplasmic domain structure, or both. This receptor heterogeneity might underlie the sharply different responses that activin can elicit in a dose- or cell-specific manner.
Attisano
L
L
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Wrana
J L
JL
Cheifetz
S
S
Massagué
J
J
D016475:3T3 Cells; D029404:Activin Receptors; D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D007265:Inhibins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins; D011494:Protein Kinases; D029404:Activin Receptors