ZFIN Image: Cheng et al., 2004, Figure 9

Image

Figure Caption

Figure 9 Model for EGF-CFC, Activin Receptors, Lefty, and TGFβ Interactions

(A) In the absence of ligands, the EGF-CFC coreceptor (solid pink) is constitutively bound to the type I receptor Alk4 (solid green).

(B) Nodal (solid blue) binds to receptor complexes consisting of EGF-CFC/Alk4 and ActRIIB (solid green).

(C) Lefty (solid yellow) sequesters the EGF-CFC coreceptor, thereby preventing Nodal binding to the receptor complexes.

(D) Subtle sequence differences determine the interaction with the EGF-CFC coreceptor and the Lefty inhibitor. Nodal and Vg1/GDF1 (solid blue) require the EGF-CFC coreceptor for signaling through ActRIIB and Alk4, while Activin (solid red) does not. Sqt^Act^β^B[loop^β^8] and Vg1^Act^β^B[loop^β^8] (solid blue with red strip) containing the loop-β8 region of ActivinβB can bind to ActRIIB and Alk4 without the EGF-CFC coreceptor and therefore cannot be blocked by Lefty. Act^{Sqt[Finger1-loop}^β^8] (solid red with two blue strips) requires the coreceptor for receptor complex binding and can be inhibited by Lefty.

Acknowledgments

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