Chordin-like CR domains and the regulation of evolutionarily conserved extracellular signaling systems.
In fruit flies as well as in humans the Short gastrulation (Sog)/Chordin protein functions as an antagonist of the signaling of decapentaplegic (Dpp)/bone morphogenetic protein (BMP) in the extracellular space. Such antagonism inhibits Dpp/BMP signaling by blocking its binding to the receptor. Modulation of Dpp/BMP signaling is phylogenetically conserved and is a key step for the establishment of the dorso-ventral axis in vertebrates and invertebrates. Molecular studies have shown that the inhibitory activity of Chordin on BMP resides in specific cysteine-rich (CR) domains. Interestingly, Chordin-like CR domains are present in a growing number of extracellular proteins, several of which appear to be involved in BMP signaling regulation. We review here the conservation of the Chordin and Sog proteins, and in particular their functional domain, the CR domain. We discuss how the study of CR domains may provide a general mechanism for the regulation of growth factor signaling in the extracellular space.
Garcia Abreu
José
J
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
Coffinier
Catherine
C
Larraín
Juan
J
Oelgeschläger
Michael
M
De Robertis
E M
EM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D005110:Extracellular Space / Q000502:physiology; D006023:Glycoproteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010802:Phylogeny; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; C054234:chordin