TGF beta signals through a heteromeric protein kinase receptor complex.
Transforming growth factor beta (TGF beta) binds with high affinity to the type II receptor, a transmembrane protein with a cytoplasmic serine/threonine kinase domain. We show that the type II receptor requires both its kinase activity and association with another TGF beta-binding protein, the type I receptor, to signal growth inhibition and early gene responses. Receptors I and II associate as interdependent components of a heteromeric complex: receptor I requires receptor II to bind TGF beta, and receptor II requires receptor I to signal. This mode of operation points to fundamental differences between this receptor and the protein-tyrosine kinase cytokine receptors.
Wrana
J L
JL
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Attisano
L
L
Cárcamo
J
J
Zentella
A
A
Doody
J
J
Laiho
M
M
Wang
X F
XF
Massagué
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D008907:Mink; D008954:Models, Biological; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D011494:Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012694:Serine; D015398:Signal Transduction; D013912:Threonine; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*
D009097:Multienzyme Complexes; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D013912:Threonine; D012694:Serine; D011494:Protein Kinases