Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors.
Transforming growth factor beta (TGF beta) and activin each bind to pairs of membrane proteins, known as receptor types I and II, that associate to form a signaling complex. We report that TSR-I and ActR-I, two human transmembrane serine/threonine kinases distantly related to TGF beta and activin type II receptors, act as type I receptors for these factors. TSR-I is a type I receptor shared by TGF beta and activin, whereas ActR-I is an activin type I receptor. ActR-I, but not TSR-I, signals a particular transcriptional response in concert with activin type II receptors. The results indicate that type I receptors are transmembrane protein kinases that associate with type II receptors to generate diverse heteromeric serine/threonine kinase complexes of different signaling capacities.
Attisano
L
L
Cell Biology and Genetics Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cárcamo
J
J
Ventura
F
F
Weis
F M
FM
Massagué
J
J
Wrana
J L
JL
D029404:Activin Receptors; D028341:Activins; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007265:Inhibins / Q000378:metabolism*; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D017931:DNA Primers; D018076:DNA, Complementary; D008024:Ligands; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors