Matters of context guide future research in TGFβ superfamily signaling

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Science Signaling  20 Oct 2015:
Vol. 8, Issue 399, pp. re10
DOI: 10.1126/scisignal.aad0416
  • Fig. 1 TGFβ and BMP signaling pathways.

    Endothelial, immune, and stem cells express the co-receptor endoglin, whereas most other cell types express the co-receptor betaglycan. Note that ACVRL1/ALK-1 can be triggered by TGFβ or by BMP9 to activate the SMAD1/5/8 pathway. Both receptors can also signal to non-SMAD pathways indicated in green shaded boxes. CREDIT: P. HUEY/SCIENCE SIGNALING

  • Fig. 2 Epithelial homeostasis, EMT, and nodes of TGFβ signaling regulation.

    Cartoon shows differential regulation of TGFβ signaling at the levels of (i) ligand synthesis from the Golgi and secretion from the cell; (ii) integrin-mediated TGFβ activation from the extracellular matrix (ECM)–bound latent complex; (iii) restriction of TGFβ receptors to basolateral surface of epithelial cells, preventing activation by apically applied TGFβ; (iv) receptor recycling or (v) degradation, presumably together with ligand, through the retromer, canonical endocytic pathway, and/or clathrin-coated pits; (vi) cytoplasmic sequestration of phosphorylated SMAD2 (pSMAD2) by binding pYAP/TAZ; (vii) context-dependent transcriptional activation by pSMAD2/3, independent or dependent on YAP/TAZ (see Fig. 4). TGFβ inhibits growth in normal epithelia (left) but induces EMT during normal development and in adults during fibrosis, cancer, and in other pathological contexts. CREDIT: P. HUEY/SCIENCE SIGNALING

  • Fig. 3 Molecular structure of TGFβ and BMP9 in complex with their LAPs.

    (A and B) The tightly closed structure of latent TGFβ (A) contrasts with the open structure of dimeric “latent” BMP (B). The associated movie (movie S1) shows the capability of latent BMP9 to exist in either open or closed conformations. The latter may be fixed by coupling to the ECM. Figure and movie provided with permission by Timothy Springer, adapted from (59). CREDIT: ADAPTED FROM T. SPRINGER (59)

  • Fig. 4 pSMAD signaling can be dependent or independent of YAP/TAZ/TEAD activation.

    Schematic denotes possible modes of interaction between YAP/TAZ/TEAD and pSMAD2 at the level of transcription within EpH4 cells, as described by Attisano (with permission to quote unpublished concepts). CREDIT: P. HUEY/SCIENCE SIGNALING

  • Table 1 General specificity of ligands and receptors in the TGFβ superfamily.

    Brackets and arrows indicate binding partners. The type I receptors show more promiscuity for ligand binding than do the type II receptors.

Supplementary Materials

  • Supplementary Materials for:

    Matters of context guide future research in TGFβ superfamily signaling

    Rosemary J. Akhurst* and Richard W. Padgett

    *Corresponding author. E-mail: rosemary.akhurst{at}

    This PDF file includes:

    • Legend for movie S1

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    Format: Adobe Acrobat PDF

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    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.mp4 format). Dynamics of latent BMP9 conformation.

    Citation: R. J. Akhurst, R. W. Padgett, Matters of context guide future research in TGFβ superfamily signaling. Sci. Signal. 8, re10 (2015).

    © 2015 American Association for the Advancement of Science

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