Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells

Wang, Jia; Sinnett‐Smith, James; Stevens, Jan V.; Young, Steven H.; Rozengurt, Enrique

doi:10.1074/jbc.m115.711275

Cited by 41 publications

(50 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, such an approach markedly interfered with the transdifferentiation of NB4 cells into neutrophil‐like cells (data not shown) and prevented further experiments. Therefore, we performed all further experiments using 2 small molecule PKD inhibitors, CRT0066101 and KB‐NB‐142‐70, respectively. Specificity of both inhibitors has been described previously.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

PKD regulates actin polymerization, neutrophil deformability, and transendothelial migration in response to fMLP and trauma

Wille

Eiseler

Langenberger

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Neutrophils are important mediators of the innate immune defense and of the host response to a physical trauma. Because aberrant infiltration of injured sites by neutrophils was shown to cause adverse effects after trauma, we investigated how neutrophil infiltration could be modulated at the cellular level. Our data indicate that protein kinase D (PKD) is a vital regulator of neutrophil transmigration. PKD phosphorylates the Cofilin-phosphatase Slingshot-2L (SSH-2L). SSH-2L in turn dynamically regulates Cofilin activity and actin polymerization in response to a chemotactic stimulus for neutrophils, for example, fMLP. Here, we show that inhibition of PKD by two specific small molecule inhibitors results in broad, unrestricted activation of Cofilin and strongly increases the F-actin content of neutrophils even under basal conditions. This phenotype correlates with a significantly impaired neutrophil deformability as determined by optical stretcher analysis. Consequently, inhibition of PKD impaired chemotaxis as shown by reduced extravasation of neutrophils. Consequently, we demonstrate that transendothelial passage of both, neutrophil-like NB4 cells and primary PMNs recovered from a hemorrhagic shock trauma model was significantly reduced. Thus, inhibition of PKD may represent a promising modulator of the neutrophil response to trauma.

show abstract

Section: Resultsmentioning

confidence: 99%

“…inhibitors, CRT0066101[64][65][66] and KB-NB-142-70,66,67 respectively. Specificity of both inhibitors has been described previously.…”

mentioning

confidence: 99%

PKD regulates actin polymerization, neutrophil deformability, and transendothelial migration in response to fMLP and trauma

Wille

Eiseler

Langenberger

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…6 C, D). Recently, we implicated the PKD family in the regulation of YAP/TEAD activity in intestinal epithelial cells (25) but the role of the PKDs in YAP activation in response to growth-promoting factors in PDAC cells has not been examined. Consequently, we next determined whether the PKDs contribute to mediate YAP activation in PDAC cells challenged with neurotensin and insulin.…”

Section: Resultsmentioning

confidence: 99%

“…The transcriptional co-activators Y es- A ssociated P rotein (YAP) and WW-domain-containing T ranscriptional co- A ctivator with PD Z -binding motif (TAZ) are major downstream effectors of the Hippo pathway and novel sensors of insulin, GPCR and Ras signaling (22–25). The YAP/TAZ pathway, originally identified in Drosophila , is attracting intense attention as a key regulator of development, organ-size, tissue regeneration and tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Insulin Receptor and GPCR Crosstalk Stimulates YAP via PI3K and PKD in Pancreatic Cancer Cells

Hao

Zhao

et al. 2017

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

We examined the impact of crosstalk between the insulin receptor (INSR) and G protein-coupled receptor (GPCR) signaling pathways on the regulation of Yes-associated Protein (YAP) localization, phosphorylation and transcriptional activity in the context of human pancreatic ductal adenocarcinoma (PDAC). Stimulation of PANC-1 or MiaPaCa-2 cells with insulin and neurotensin, a potent mitogenic combination of agonists for these cells, promoted striking YAP nuclear localization and decreased YAP phosphorylation at Ser127 and Ser397. Challenging PDAC cells with either insulin or neurotensin alone modestly induced the expression of YAP/TEAD-regulated genes, including Connective Tissue Growth Factor (CTGF), Cysteine-rich angiogenic inducer 61 (CYR61) and CXCL5 whereas the combination of neurotensin and insulin induced a marked increase in the level of expression of these genes. In addition, siRNA-mediated knockdown of YAP/TAZ prevented the increase in the expression of these genes. A small-molecule inhibitor (A66), selective for the p110α subunit of PI3K, abrogated the increase in phosphatidylinositol 3,4,5-trisphosphate (PIP3) production and the expression of CTGF, CYR61 and CXCL5 induced by neurotensin and insulin. Furthermore, treatment of PDAC cells with protein kinase D (PKD) family inhibitors (CRT0066101 or kb NB 142-70) or with siRNAs targeting the PKD family prevented the increase of CTGF, CYR61 and CXCL5 mRNA levels in response to insulin and neurotensin stimulation. Thus, PI3K and PKD mediate YAP activation in response to insulin and neurotensin in pancreatic cancer cells.

show abstract

“…VP damages the bond and inactivates YAP (Yi et al, ; Zhao et al, ). Dephosphorylated YAP translocates into the nucleus and interacts with the TEAD family members to induce its target genes, including connective tissue growth factor (CTGF) and cysteine‐rich angiogenic inducer 61 (Cyr61) (Feng et al, ; Oudhoff et al, ; Sudol, ; Wang, Sinnett Smith, Stevens, Young, & Rozengurt, ). In this study, our data showed that Bu up‐regulated YAP expression and promoted YAP nuclear import.…”

Section: Discussionmentioning

confidence: 99%

Butyrate stimulates the growth of human intestinal smooth muscle cells by activation of yes‐associated protein

Dai

Yan²,

Xiao³

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Intestinal smooth muscle cells play a critical role in the remodeling of intestinal structure and functional adaptation after bowel resection. Recent studies have shown that supplementation of butyrate (Bu) contributes to the compensatory expansion of a muscular layer of the residual intestine in a rodent model of short-bowel syndrome (SBS). However, the underlying mechanism remains elusive. In this study, we found that the growth of human intestinal smooth muscle cells (HISMCs) was significantly stimulated by Bu via activation of Yes-Associated Protein (YAP). Incubation with 0.5 mM Bu induced a distinct proliferative effect on HISMCs, as indicated by the promotion of cell cycle progression and increased DNA replication. Notably, YAP silencing by RNA interference or its specific inhibitor significantly abolished the proliferative effect of Bu on HISMCs. Furthermore, Bu induced YAP expression and enhanced the translocation of YAP from the cytoplasm to the nucleus, which led to changes in the expression of mitogenesis genes, including TEAD1, TEAD4, CTGF, and Cyr61. These results provide evidence that Bu stimulates the growth of human intestinal muscle cells by activation of YAP, which may be a potential treatment for improving intestinal adaptation.

show abstract

Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells

Cited by 41 publications

References 74 publications

PKD regulates actin polymerization, neutrophil deformability, and transendothelial migration in response to fMLP and trauma

PKD regulates actin polymerization, neutrophil deformability, and transendothelial migration in response to fMLP and trauma

Insulin Receptor and GPCR Crosstalk Stimulates YAP via PI3K and PKD in Pancreatic Cancer Cells

Butyrate stimulates the growth of human intestinal smooth muscle cells by activation of yes‐associated protein

Contact Info

Product

Resources

About