scholarly journals Protein Kinase D1 attenuates tumorigenesis in colon cancer by modulating β-catenin/T cell factor activity

Oncotarget ◽  
2014 ◽  
Vol 5 (16) ◽  
pp. 6867-6884 ◽  
Author(s):  
Vasudha Sundram ◽  
Aditya Ganju ◽  
Joshua E. Hughes ◽  
Sheema Khan ◽  
Subhash C. Chauhan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Protein Kinase ◽  
Factor Activity ◽  
Protein Kinase D1 ◽  
T Cell Factor

scholarly journals Activation of Hematopoietic Progenitor Kinase 1 Involves Relocation, Autophosphorylation, and Transphosphorylation by Protein Kinase D1

2005 ◽  
Vol 25 (6) ◽  
pp. 2364-2383 ◽  
Author(s):  
Rüdiger Arnold ◽  
Irene M. Patzak ◽  
Brit Neuhaus ◽  
Sadia Vancauwenbergh ◽  
André Veillette ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Hematopoietic Progenitor ◽  
Kinase Activation ◽  
Protein Kinase D1 ◽  
Enzymatic Activation ◽  
Antigen Presenting

ABSTRACT Adaptive immune signaling can be coupled to stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and NF-κB activation by the hematopoietic progenitor kinase 1 (HPK1), a mammalian hematopoiesis-specific Ste20 kinase. To gain insight into the regulation of leukocyte signal transduction, we investigated the molecular details of HPK1 activation. Here we demonstrate the capacity of the Src family kinase Lck and the SLP-76 family adaptor protein Clnk (cytokine-dependent hematopoietic cell linker) to induce HPK1 tyrosine phosphorylation and relocation to the plasma membrane, which in lymphocytes results in recruitment of HPK1 to the contact site of antigen-presenting cell (APC)-T-cell conjugates. Relocation and clustering of HPK1 cause its enzymatic activation, which is accompanied by phosphorylation of regulatory sites in the HPK1 kinase activation loop. We show that full activation of HPK1 is dependent on autophosphorylation of threonine 165 and phosphorylation of serine 171, which is a target site for protein kinase D (PKD) in vitro. Upon T-cell receptor stimulation, PKD robustly augments HPK1 kinase activity in Jurkat T cells and enhances HPK1-driven SAPK/JNK and NF-κB activation; conversely, antisense down-regulation of PKD results in reduced HPK1 activity. Thus, activation of major lymphocyte signaling pathways via HPK1 involves (i) relocation, (ii) autophosphorylation, and (iii) transphosphorylation of HPK1 by PKD.

Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the ??-catenin/T-cell factor signaling

2006 ◽  
Vol 17 (7) ◽  
pp. 753-762 ◽  
Author(s):  
Debing Xiang ◽  
Dong Wang ◽  
Yujun He ◽  
Jiayin Xie ◽  
Zhaoyang Zhong ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Cancer Cells ◽  
Caffeic Acid ◽  
Growth Arrest ◽  
Caffeic Acid Phenethyl Ester ◽  
Colon Cancer Cells ◽  
T Cell Factor

scholarly journals Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells

2015 ◽  
Vol 35 (20) ◽  
pp. 3471-3490 ◽  
Author(s):  
Linh M. Vuong ◽  
Karthikeyani Chellappa ◽  
Joseph M. Dhahbi ◽  
Jonathan R. Deans ◽  
Bin Fang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
Tumor Growth ◽  
Hct116 Cell ◽  
Xenograft Model ◽  
Global Changes ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
T Cell Factor ◽  
Hepatocyte Nuclear Factor 4Α

The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) is tumor suppressive in the liver but amplified in colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy is due to different HNF4α isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human colon cancer (HCT116) cell lines that express either the P1-driven (HNF4α2) or P2-driven (HNF4α8) isoform and analyzed them for tumor growth and global changes in gene expression (transcriptome sequencing [RNA-seq] and chromatin immunoprecipitation sequencing [ChIP-seq]). The results show that while HNF4α2 acts as a tumor suppressor in the HCT116 tumor xenograft model, HNF4α8 does not. Each isoform regulates the expression of distinct sets of genes and recruits, colocalizes, and competes in a distinct fashion with the Wnt/β-catenin mediator T-cell factor 4 (TCF4) at CTTTG motifs as well as at AP-1 motifs (TGAXTCA). Protein binding microarrays (PBMs) show that HNF4α and TCF4 share some but not all binding motifs and that single nucleotide polymorphisms (SNPs) in sites bound by both HNF4α and TCF4 can alter binding affinityin vitro, suggesting that they could play a role in cancer susceptibilityin vivo. Thus, the HNF4α isoforms play distinct roles in colon cancer, which could be due to differential interactions with the Wnt/β-catenin/TCF4 and AP-1 pathways.

Abstract 2907: Protein Kinase D1 expression attenuates colon cancer progression

2011 ◽  
Author(s):  
Joshua E. Hughes ◽  
Sarah Radel ◽  
Vasudha Sundram ◽  
Tyler N. Jepperson ◽  
Michael R.D Koch ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Protein Kinase ◽  
Cancer Progression ◽  
Protein Kinase D1 ◽  
Colon Cancer Progression

scholarly journals Protein Kinase D1 Phosphorylates HDAC7 and Induces Its Nuclear Export after T-cell Receptor Activation

2004 ◽  
Vol 280 (14) ◽  
pp. 13762-13770 ◽  
Author(s):  
Maribel Parra ◽  
Herbert Kasler ◽  
Timothy A. McKinsey ◽  
Eric N. Olson ◽  
Eric Verdin
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
T Cell Receptor ◽  
Nuclear Export ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Protein Kinase D1

scholarly journals The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer

2012 ◽  
Vol 31 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Bethany M. Bush ◽  
Ashton T. Brock ◽  
Jiayue A. Deng ◽  
Ronald A. Nelson ◽  
Takita Felder Sumter
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
High Mobility ◽  
High Mobility Group ◽  
T Cell Factor

The Metastasis-Associated Gene S100A4 Is a Novel Target of β-catenin/T-cell Factor Signaling in Colon Cancer

2006 ◽  
Vol 131 (5) ◽  
pp. 1486-1500 ◽  
Author(s):  
Ulrike Stein ◽  
Franziska Arlt ◽  
Wolfgang Walther ◽  
Janice Smith ◽  
Todd Waldman ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cell ◽  
T Cell Factor ◽  
Novel Target ◽  
Metastasis Associated Gene

scholarly journals Interaction of FOXO with β-Catenin Inhibits β-Catenin/T Cell Factor Activity

2008 ◽  
Vol 283 (14) ◽  
pp. 9224-9230 ◽  
Author(s):  
Diana Hoogeboom ◽  
Marieke A. G. Essers ◽  
Paulien E. Polderman ◽  
Erik Voets ◽  
Lydia M. M. Smits ◽  
...  
Keyword(s):  
T Cell ◽  
Factor Activity ◽  
T Cell Factor
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