scholarly journals Palmitoylation of Cytoskeleton Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling

2009 ◽  
Vol 20 (5) ◽  
pp. 1454-1463 ◽  
Author(s):  
Sonia L. Planey ◽  
Susan K. Keay ◽  
Chen-Ou Zhang ◽  
David A. Zacharias
Keyword(s):  
Epithelial Cells ◽  
Cellular Proliferation ◽  
Phosphorylated Protein ◽  
Normal Bladder ◽  
High Affinity Receptor ◽  
Palmitoyl Acyltransferase ◽  
Cellular Behaviors ◽  
Affinity Receptor ◽  
Induced Changes

Previously, we identified cytoskeleton-associated protein 4 (CKAP4) as a major substrate of the palmitoyl acyltransferase, DHHC2, using a novel proteomic method called palmitoyl-cysteine identification, capture and analysis (PICA). CKAP4 is a reversibly palmitoylated and phosphorylated protein that links the ER to the cytoskeleton. It is also a high-affinity receptor for antiproliferative factor (APF), a small sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). The role of DHHC2-mediated palmitoylation of CKAP4 in the antiproliferative response of HeLa and normal bladder epithelial cells to APF was investigated. Our data show that siRNA-mediated knockdown of DHHC2 and consequent suppression of CKAP4 palmitoylation inhibited the ability of APF to regulate cellular proliferation and blocked APF-induced changes in the expression of E-cadherin, vimentin, and ZO-1 (genes known to play a role in cellular proliferation and tumorigenesis). Immunocytochemistry revealed that CKAP4 palmitoylation by DHHC2 is required for its trafficking from the ER to the plasma membrane and for its nuclear localization. These data suggest an important role for DHHC2-mediated palmitoylation of CKAP4 in IC and in opposing cancer-related cellular behaviors and support the idea that DHHC2 is a tumor suppressor.

scholarly journals Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
David A. Zacharias ◽  
Matthew Mullen ◽  
Sonia Lobo Planey
Keyword(s):  
Signal Transduction ◽  
Cellular Proliferation ◽  
Nuclear Translocation ◽  
Transmembrane Protein ◽  
Serine Phosphorylation ◽  
Dependent Manner ◽  
High Affinity Receptor ◽  
Surface Localization ◽  
Palmitoyl Acyltransferase ◽  
Induced Changes

Cytoskeleton-associated protein 4 (CKAP4) is a reversibly palmitoylated and phosphorylated transmembrane protein that functions as a high-affinity receptor for antiproliferative factor (APF)—a sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). Palmitoylation of CKAP4 by the palmitoyl acyltransferase, DHHC2, is required for its cell surface localization and subsequent APF signal transduction; however, the mechanism for APF signal transduction by CKAP4 is unknown. In this paper, we demonstrate that APF treatment induces serine phosphorylation of residues S3, S17, and S19 of CKAP4 and nuclear translocation of CKAP4. Additionally, we demonstrate that CKAP4 binds gDNA in a phosphorylation-dependent manner in response to APF treatment, and that a phosphomimicking, constitutively nonpalmitoylated form of CKAP4 localizes to the nucleus, binds DNA, and mimics the inhibitory effects of APF on cellular proliferation. These results reveal a novel role for CKAP4 as a downstream effecter for APF signal transduction.

CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1962-1969 ◽  
Author(s):  
Luisa Granziero ◽  
Paola Circosta ◽  
Cristina Scielzo ◽  
Elisa Frisaldi ◽  
Stefania Stella ◽  
...  
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Follicular Dendritic Cells ◽  
Growth And Survival ◽  
High Affinity Receptor ◽  
Activated T Lymphocytes ◽  
Affinity Receptor

Growth and survival of chronic B-cell tumors are favored by the malignant cell's capacity to respond to selected microenvironmental stimuli provided by nontumoral bystander cells. To investigate which mechanisms operate in these crosstalks and whether they are malignancy-related or reproduce the mechanisms used by normal B cells we have studied the expression and functional role of semaphorin CD100 (now called Sema4D) in chronic lymphocytic leukemia (CLL) cells and normal CD5+ B cells. We demonstrate here that (1) leukemic and normal CD5+ B lymphocytes uniformly express CD100; (2) the CD100 high-affinity receptor Plexin-B1 is expressed by bone marrow stromal cells, follicular dendritic cells, and activated T lymphocytes, and is thus available to CD100+ lymphocytes in different specific microenvironments; and (3) upon interaction between CD100 and Plexin-B1 both CLL and normal CD5+ B cells increase their proliferative activity and extend their life span. These findings establish that Plexin-B1 is an easily accessible receptor for CD100 within the immune system. The encounter of CD100+ leukemic cells with Plexin-B1 may promote the proliferation and survival of malignant cells. The crosstalk operated by the CD100/Plexin-B1 interaction is not malignancy related but reproduces a mechanism used by normal CD5+ B cells.

Assessing the role of Asp 194 in the transmembrane domains of the α-chain of the high-affinity receptor complex for immunoglobulin E in signal transduction

2010 ◽  
Vol 48 (1-3) ◽  
pp. 128-136 ◽  
Author(s):  
Amir Rashid ◽  
Marco W. Iodice ◽  
Kathleen M. Carroll ◽  
Jonathan E.M. Housden ◽  
Michael Hunter ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Immunoglobulin E ◽  
Transmembrane Domains ◽  
Receptor Complex ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Α Chain

scholarly journals Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

2011 ◽  
Vol 208 (11) ◽  
pp. 2225-2236 ◽  
Author(s):  
Adeline Porcherie ◽  
Cedric Mathieu ◽  
Roger Peronet ◽  
Elke Schneider ◽  
Julien Claver ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Critical Role ◽  
Experimental Cerebral Malaria ◽  
Effector Cells ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
The Brain ◽  
Malaria Severity

The role of the IgE–FcεRI complex in malaria severity in Plasmodium falciparum–hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-expressing effector cells, are not involved in disease as mast cell–deficient and basophil-depleted mice developed a disease similar to wild-type mice. However, we show the emergence of an FcεRI+ neutrophil population, which is not observed in mice hosting a non–ECM-inducing PbNK65 parasite strain. Depletion of this FcεRI+ neutrophil population prevents ECM, whereas transfer of this population into FcεRIα-KO mice restores ECM susceptibility. FcεRI+ neutrophils preferentially home to the brain and induce elevated levels of proinflammatory cytokines. These data define a new pathogenic mechanism of ECM and implicate an FcεRI-expressing neutrophil subpopulation in malaria disease severity.

Expression of the High-affinity Receptor for IgE on Bronchial Epithelial Cells of Asthmatics

1998 ◽  
Vol 19 (1) ◽  
pp. 92-97 ◽  
Author(s):  
Alison M. Campbell ◽  
Isabelle Vachier ◽  
Pascal Chanez ◽  
Antonio M. Vignola ◽  
Bernard Lebel ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor
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