scholarly journals Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells

2008 ◽  
Vol 121 (5) ◽  
pp. 644-654 ◽  
Author(s):  
F. A. Wald ◽  
A. S. Oriolo ◽  
A. Mashukova ◽  
N. L. Fregien ◽  
A. H. Langshaw ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Atypical Protein Kinase C ◽  
Atypical Protein Kinase ◽  
Kinase C ◽  
Apical Domain ◽  
Protein Kinase C Iota

scholarly journals Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling

2015 ◽  
Vol 26 (20) ◽  
pp. 3578-3595 ◽  
Author(s):  
Andrew Archibald ◽  
Maia Al-Masri ◽  
Alyson Liew-Spilger ◽  
Luke McCaffrey
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
3D Culture ◽  
Cell Junctions ◽  
Nuclear Accumulation ◽  
Cell Phenotype ◽  
Atypical Protein Kinase C ◽  
Atypical Protein Kinase ◽  
Kinase C

Epithelial cells are major sites of malignant transformation. Atypical protein kinase C (aPKC) isoforms are overexpressed and activated in many cancer types. Using normal, highly polarized epithelial cells (MDCK and NMuMG), we report that aPKC gain of function overcomes contact inhibited growth and is sufficient for a transformed epithelial phenotype. In 2D cultures, aPKC induced cells to grow as stratified epithelia, whereas cells grew as solid spheres of nonpolarized cells in 3D culture. aPKC associated with Mst1/2, which uncoupled Mst1/2 from Lats1/2 and promoted nuclear accumulation of Yap1. Of importance, Yap1 was necessary for aPKC-mediated overgrowth but did not restore cell polarity defects, indicating that the two are separable events. In MDCK cells, Yap1 was sequestered to cell–cell junctions by Amot, and aPKC overexpression resulted in loss of Amot expression and a spindle-like cell phenotype. Reexpression of Amot was sufficient to restore an epithelial cobblestone appearance, Yap1 localization, and growth control. In contrast, the effect of aPKC on Hippo/Yap signaling and overgrowth in NMuMG cells was independent of Amot. Finally, increased expression of aPKC in human cancers strongly correlated with increased nuclear accumulation of Yap1, indicating that the effect of aPKC on transformed growth by deregulating Hippo/Yap1 signaling may be clinically relevant.

scholarly journals Involvement of the ERK Signaling Cascade in Protein Kinase C-mediated Cell Cycle Arrest in Intestinal Epithelial Cells

2003 ◽  
Vol 279 (10) ◽  
pp. 9233-9247 ◽  
Author(s):  
Jennifer A. Clark ◽  
Adrian R. Black ◽  
Olga V. Leontieva ◽  
Mark R. Frey ◽  
Marybeth A. Pysz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Erk Signaling ◽  
Signaling Cascade ◽  
Intestinal Epithelial ◽  
Cycle Arrest ◽  
Kinase C

scholarly journals Atypical protein kinase C iota (PKCλ/ι) ensures mammalian development by establishing the maternal–fetal exchange interface

2020 ◽  
Vol 117 (25) ◽  
pp. 14280-14291
Author(s):  
Bhaswati Bhattacharya ◽  
Pratik Home ◽  
Avishek Ganguly ◽  
Soma Ray ◽  
Ananya Ghosh ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mammalian Development ◽  
Atypical Protein Kinase C ◽  
Differentiation Potential ◽  
Human Trophoblast ◽  
Atypical Protein Kinase ◽  
Kinase C ◽  
Trophoblast Stem ◽  
Protein Kinase C Iota

In utero mammalian development relies on the establishment of the maternal–fetal exchange interface, which ensures transportation of nutrients and gases between the mother and the fetus. This exchange interface is established via development of multinucleated syncytiotrophoblast cells (SynTs) during placentation. In mice, SynTs develop via differentiation of the trophoblast stem cell-like progenitor cells (TSPCs) of the placenta primordium, and in humans, SynTs are developed via differentiation of villous cytotrophoblast (CTB) progenitors. Despite the critical need in pregnancy progression, conserved signaling mechanisms that ensure SynT development are poorly understood. Herein, we show that atypical protein kinase C iota (PKCλ/ι) plays an essential role in establishing the SynT differentiation program in trophoblast progenitors. Loss of PKCλ/ι in the mouse TSPCs abrogates SynT development, leading to embryonic death at approximately embryonic day 9.0 (E9.0). We also show that PKCλ/ι-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. PKCλ/ι is selectively expressed in the first-trimester CTBs of a developing human placenta. Furthermore, loss of PKCλ/ι in CTB-derived human trophoblast stem cells (human TSCs) impairs their SynT differentiation potential both in vitro and after transplantation in immunocompromised mice. Our mechanistic analyses indicate that PKCλ/ι signaling maintains expression of GCM1, GATA2, and PPARγ, which are key transcription factors to instigate SynT differentiation programs in both mouse and human trophoblast progenitors. Our study uncovers a conserved molecular mechanism, in which PKCλ/ι signaling regulates establishment of the maternal–fetal exchange surface by promoting trophoblast progenitor-to-SynT transition during placentation.

scholarly journals Protein kinase C-mediated phosphorylation of RKIP regulates inhibition of Na-alanine cotransport by leukotriene D4in intestinal epithelial cells

2014 ◽  
Vol 307 (11) ◽  
pp. C1010-C1016 ◽  
Author(s):  
Subha Arthur ◽  
Uma Sundaram
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Intracellular Signaling ◽  
Kinase Inhibitor ◽  
Intestinal Epithelial Cells ◽  
Receptor Activation ◽  
Intestinal Epithelial ◽  
Kinase C ◽  
Pka Pathway

Leukotriene D4(LTD4) is an important immune inflammatory mediator that is known to be elevated in the mucosa of chronically inflamed intestine and alter nutrient absorption. LTD4inhibits Na-alanine cotransport in intestinal epithelial cells by decreasing the affinity of the cotransporter ASCT1. LTD4is known to increase intracellular Ca++and cAMP concentrations. However, the intracellular signaling mechanism of LTD4-mediated ASCT1 inhibition is unknown. In the present study, pretreatment with calcium chelator BAPTA-AM or inhibition of Ca++-dependent protein kinase C (PKC), specifically PKCα, resulted in the reversal of LTD4-mediated inhibition of ASCT1, revealing the involvement of the Ca++-activated PKC pathway. PKCα is known to phosphorylate Raf kinase inhibitor protein (RKIP), thus activating its downstream signaling pathway. Immunoblotting with anti-RKIP-Ser153antibody showed an increase in phosphorylation levels of RKIP in LTD4-treated cells. Downregulation of endogenous RKIP showed no decrease in ASCT1 activity by LTD4, thus confirming its involvement in ASCT1 regulation. Phosphorylation of RKIP by PKC is known to activate different signaling pathways, and in this study it was found to activate cAMP-activated protein kinase A (PKA) pathway. Although protein abundance of ASCT1 was not altered in any of the experimental conditions, there was an increase in the levels of phosphothreonine in ASCT1 protein, thus showing that phosphorylation changes were responsible for the altered affinity of ASCT1 by LTD4. In conclusion, LTD4 inhibits ASCT1 through PKC-mediated phosphorylation of RKIP, leading to the subsequent activation of PKA pathway, possibly through β2-andrenergic receptor activation.

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