Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

Adler, Jacob J.; Johnson, Derrick E.; Heller, Brigitte; Bringman, Lauren R.; Ranahan, William P.; Conwell, Michael; Sun, Yangying; Hudmon, Andy; Wells, Clark D.

doi:10.1073/pnas.1308236110

Cited by 128 publications

(140 citation statements)

References 42 publications

(59 reference statements)

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“…Further study is needed to address this issue. During the preparation of this manuscript, there were three papers that also show that Amot is phosphorylated by LATS (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Actin-binding and Cell Proliferation Activities of Angiomotin Family Members Are Regulated by Hippo Pathway-mediated Phosphorylation

Chan

Lim

Guo

et al. 2013

Journal of Biological Chemistry

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Background: LATS kinase, one of the core kinases of Hippo pathway, phosphorylates and inactivates the downstream coactivator YAP/TAZ. Results: The angiomotin (Amot) family members are phosphorylated by LATS kinase. Conclusion: Phosphorylation of Amots by LATS kinase inhibits actin-binding, stabilizes Amot, and inhibits cell proliferation. Significance: Besides phosphorylating YAP/TAZ, LATS kinase may phosphorylate other components of the Hippo pathway.

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“…Further study is needed to address this issue. During the preparation of this manuscript, there were three papers that also show that Amot is phosphorylated by LATS (22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Actin-binding and Cell Proliferation Activities of Angiomotin Family Members Are Regulated by Hippo Pathway-mediated Phosphorylation

Chan

Lim

Guo

et al. 2013

Journal of Biological Chemistry

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“…Other molecules and molecular interactions also appear to diverge between Drosophila and vertebrates (Bossuyt et al, 2013). Notably, the vertebrate junctionassociated adaptor protein angiomotin (Amot), which was found to have key roles in mammalian Hippo-YAP signaling (Zhao et al, 2011;Adler et al, 2013;Hirate et al, 2013), has no homologue in Drosophila. Nonetheless, most of the downstream core components of the Hippo-YAP signaling pathway, as well as some upstream regulators such as Merlin/NF2, function similarly in Drosophila and vertebrates.…”

Section: Interacting Upstream Modules Regulate Hippo-yap Signalingmentioning

confidence: 99%

The Hippo-YAP signaling pathway and contact inhibition of growth

Gumbiner

Kim

2014

Journal of Cell Science

280

188

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The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherincatenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZdependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factormediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes.

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“…8A, enhanced level of nuclearly localized YAP was detected by 15 min following endothelial cell binding to collagen peptide P-2 as compared with P-1. The differential nuclear localization of YAP was not consistently detected at later times points, likely due to the lack of serum or growth factors during the time course of binding (49). To confirm and quantify the enhanced nuclear accumulation of YAP, Western blot analysis was carried out.…”

Section: Cellular Interactions With Rgdkge-containing Peptide Enhancementioning

confidence: 99%

“…Moreover, YAP has been shown to play a functional role in regulating angiogenesis (48,49) and compounds known to inhibit YAP inhibit angiogenesis in the chick CAM model (50,51). To this end, we identified an siRNA capable of significantly reducing the relative levels of YAP following in vivo transfection of CAM tissues (Fig.…”

Section: Cellular Interactions With Rgdkge-containing Peptide Enhancementioning

confidence: 99%

Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway

Ames

Contois

Caron

et al. 2016

Journal of Biological Chemistry

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Extracellular matrix (ECM) remodeling regulates angiogenesis. However, the precise mechanisms by which structural changes in ECM proteins contribute to angiogenesis are not fully understood. Integrins are molecules with the ability to detect compositional and structural changes within the ECM and integrate this information into a network of signaling circuits that coordinate context-dependent cell behavior. The role of integrin ␣v␤3 in angiogenesis is complex, as evidence exists for both positive and negative functions. The precise downstream signaling events initiated by ␣v␤3 may depend on the molecular characteristics of its ligands. Here, we identified an RGD-containing cryptic collagen epitope that is generated in vivo. Surprisingly, rather than inhibiting ␣v␤3 signaling, this collagen epitope promoted ␣v␤3 activation and stimulated angiogenesis and inflammation. An antibody directed to this RGDKGE epitope but not other RGD collagen epitopes inhibited angiogenesis and inflammation in vivo. The selective ability of this RGD epitope to promote angiogenesis and inflammation depends in part on its flanking KGE motif. Interestingly, a subset of macrophages may represent a physiologically relevant source of this collagen epitope. Here, we define an endothelial cell mechano-signaling pathway in which a cryptic collagen epitope activates ␣v␤3 leading to an Src and p38 MAPK-dependent cascade that leads to nuclear accumulation of Yes-associated protein (YAP) and stimulation of endothelial cell growth. Collectively, our findings not only provide evidence for a novel mechano-signaling pathway, but also define a possible therapeutic strategy to control ␣v␤3 signaling by targeting a proangiogenic and inflammatory ligand of ␣v␤3 rather than the receptor itself.

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Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases

Cited by 128 publications

References 42 publications

Actin-binding and Cell Proliferation Activities of Angiomotin Family Members Are Regulated by Hippo Pathway-mediated Phosphorylation

Actin-binding and Cell Proliferation Activities of Angiomotin Family Members Are Regulated by Hippo Pathway-mediated Phosphorylation

The Hippo-YAP signaling pathway and contact inhibition of growth

Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway

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