The Nodal signaling pathway. Genetic interaction and co-Immunoprecipitation (co-IP) studies have shown that the
TGFß family ligand Nodal (orange) interacts with the extracellular domains of type
I Activin receptor-like kinases, including ALK4 and/or ALK7 (light blue), and type
II Activin receptor kinases, including ACTRIIA and/or ACTRIIB (dark blue). Simultaneous
binding of Nodal to both receptors initiates a phosphorylation cascade that leads
to translocation of phosphorylated Smad2 or Smad3 (light green) transcription factors
to the nucleus and expression of Nodal target genes. Nodal signaling also requires
the EGF-CFC 'co-receptors' Cripto-1 and/or Cryptic (purple) during embryonic development.
Co-IP studies have shown that EGF-CFC co-receptors interact with Nodal, but how they
mediate Nodal signaling is not well understood. The secreted protein Cerberus (light
orange) binds Nodal and inhibits Nodal signaling.
