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Vol. 12, No. 14, pp. 2144-2152, July 15, 1998
signal transduction
1 Cell Biology Program and
2 Cellular
Biochemistry and Biophysics Program, Howard Hughes Medical Institute,
Memorial Sloan-Kettering Cancer Center, New York, New York 10021 USA
Signal transduction by the TGF-
family involves sets of
receptor serine/threonine kinases, Smad proteins that act
as receptor substrates, and Smad-associated transcription factors that
target specific genes. We have identified discrete structural elements that dictate the selective interactions between receptors and Smads and
between Smads and transcription factors in the TGF- and BMP
pathways. A cluster of four residues in the L45 loop of the type I
receptor kinase domain, and a matching set of two residues in the L3
loop of the Smad carboxy-terminal domain establish the specificity of
receptor-Smad interactions. A cluster of residues in the highly
exposed 
-helix 2 of the Smad carboxy-terminal domain specify the
interaction with the DNA-binding factor Fast1 and, as a result, the
gene responses mediated by the pathway. By establishing specific
interactions, these determinants keep the TGF- and BMP pathways
segregated from each other.
[Key Words:
TGF-; signal transduction; Smad
proteins; BMP pathway]
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