Abstract:
:EPHA2 receptor tyrosine kinase is overexpressed in several human cancer types and promotes malignancy. However, the mechanisms by which EPHA2 promotes tumor progression are not completely understood. Here we report that overexpression of a wild-type EPHA2, but not a signaling-defective cytoplasmic truncation mutant (DeltaC), in human mammary epithelial cells weakens E-cadherin-mediated cell-cell adhesion. Interestingly, the total level of cadherins and the composition of the adherens junction complexes were not affected, nor was the tyrosine phosphorylation of the cadherin complex components changed. By contrast, RhoA GTPase activity was significantly affected by modulating the EPHA2 activity in MCF-10A cells. Treatment with a ROCK kinase inhibitor rescued cell-cell adhesion defects in EPHA2-overexpressing cells, whereas expression of constitutively activated Rho disrupted adherens junctions in DeltaC-expressing cells. EPHA2-dependent Rho activation and destabilization of adherens junctions appeared to be regulated via a signaling pathway involving Src kinase, low molecular weight phosphotyrosine phosphatase (LMW-PTP) and p190 RhoGAP. EPHA2 interacted with both Src and LMW-PTP, and the interactions increased in EPHA2-overexpressing cells. In addition, LMW-PTP phosphatase activity was elevated, and this elevation was accompanied by a decrease in tyrosine phosphorylation of p190 RhoGAP and destabilization of cell-cell adhesion. Expression of either a dominant negative LMW-PTP mutant, C12S, or a wild-type p190 RhoGAP rescued adhesion defects in EPHA2-overexpressing cells. Together, these data suggest that EPHA2 promotes tumor malignancy through a mechanism involving RhoA-dependent destabilization of adherens junctions.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Fang WB,Ireton RC,Zhuang G,Takahashi T,Reynolds A,Chen Jdoi
10.1242/jcs.017145subject
Has Abstractpub_date
2008-02-01 00:00:00pages
358-68issue
Pt 3eissn
0021-9533issn
1477-9137pii
jcs.017145journal_volume
121pub_type
杂志文章abstract::Endothelial permeability induced by thrombin and histamine is accompanied by actin stress fibre assembly and intercellular gap formation. Here, we investigate the roles of the Rho family GTPases Rho1, Rac1 and Cdc42 in regulating endothelial barrier function, and correlate this with their effects on F-actin organizati...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::The nuclear envelope is much more than a simple barrier between nucleoplasm and cytoplasm. Nuclear envelope bridging complexes are protein complexes spanning both the inner and outer nuclear envelope membranes, thus directly connecting the cytoplasm with the nucleoplasm. In metazoans, they are involved in connecting t...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.186700
更新日期:2016-10-01 00:00:00
abstract::The structural events in the stigma and transmitting tissue of Petunia hybrida pistils that accompany compatible and incompatible intraspecific pollinations have been investigated in detail, together with the changes in reserve levels that also take place at this time. Many of these phenomena may be explained in terms...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1979-04-01 00:00:00
abstract::Cultured human erythrocytes infected with Plasmodium falciparum were studied by freeze-fracture electron microscopy. Special emphasis was placed upon the formation of the membrane surface excrescences ('knobs') found on red cells containing mature parasites. Knobs were visualized as conoid projections of the protoplas...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Proteins destined for the mitochondria travel an intricate pathway through two membranes, each with its own receptors and channels. These proteins interact with receptors via N-terminal presequences that form amphipathic helices. Generally, these helices contain abundant positive charges on one face and hydrophobic re...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00750
更新日期:2003-11-15 00:00:00
abstract::After DNA replication, cells condense their chromosomes in order to segregate them during mitosis. The condensation process as well as subsequent segregation requires phosphorylation of histone H3 at serine 10. Histone H3 phosphorylation initiates during G2 in pericentric foci prior to H3 phosphorylation in the chromo...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00
abstract::To study the influence of the non alpha-helical tail domain of keratins in filament formation, we prepared a truncated keratin 8 mutant, K8/tailless. Using site-directed in vitro mutagenesis we introduced a stop codon in the position coding for amino acid number 417 of the K8/wild-type sequence, thereby deleting 86 am...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::As previously described, a cell surface-associated adhesive factor (AF) was separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) and highly purified by chromatography. AF synthesis by the cells was investigated by means of ultrastructural immunoperoxidase cytochemistry. Its sy...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::The process of cell migration is initiated by protrusion at the leading edge of the cell, the formation of peripheral adhesions, the exertion of force on these adhesions, and finally the release of the adhesions at the rear of the cell. Focal adhesion kinase (FAK) is intimately involved in the regulation of this proce...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02380
更新日期:2005-06-15 00:00:00
abstract::Skeletal muscle is primarily composed of large myofibers containing thousands of post-mitotic nuclei distributed throughout a common cytoplasm. Protein production and localization in specialized myofiber regions is crucial for muscle function. Myonuclei differ in transcriptional activity and protein accumulation, but ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.207670
更新日期:2018-02-05 00:00:00
abstract::Cells constantly adapt to various environmental changes and stresses. The way in which nutrient and stress levels in a cell feed back to control metabolism and growth are, unsurprisingly, extremely complex, as responding with great sensitivity and speed to the 'feast or famine, slack or stress' status of its environme...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.168922
更新日期:2015-06-15 00:00:00
abstract::MAP1B is a developmentally regulated microtubule-associated phosphoprotein that regulates microtubule dynamics in growing axons and growth cones. We used mass spectrometry to map 28 phosphorylation sites on MAP1B, and selected for further study a putative primed GSK3 beta site and compared it with two nonprimed GSK3 b...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.040162
更新日期:2009-07-15 00:00:00
abstract::Different isoforms of non-muscle myosin II have different distributions in vivo, even within individual cells. In order to understand how these different distributions arise, the distribution and dynamics of non-muscle myosins IIA and myosin IIB were examined in cultured cells using immunofluorescence staining and tim...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::We have cloned and characterized a single copy C. reinhardtii gene containing an open reading frame of 333 nucleotides encoding a 12.7 kDa protein. The novel protein, DIP13, exhibits 60% identity with two mammalian proteins, human NA14 and an unnamed mouse protein. Homologous sequences are also present in several prot...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00337
更新日期:2003-04-15 00:00:00
abstract::In adherent cells, the relevance of a physical mechanotransduction pathway provided by the perinuclear actin cap stress fibers has recently emerged. Here, we investigate the impact of a functional actin cap on the cellular adaptive response to topographical cues and uniaxial cyclic strain. Lmna-deficient fibroblasts a...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.184838
更新日期:2017-02-15 00:00:00
abstract::Adaptors are the membrane-binding components of clathrin-coated vesicles. The interaction of the trans-Golgi coat adaptor AP1 with membrane-associated proteins was analyzed by affinity chromatography. Proteins of 83 and 52 kDa bound specifically to the core domain of AP1 and showed no interaction with AP2 or other cla...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::Microinjected GTP gamma S revealed three distinct steps in the exocytic transport of the temperature sensitive glycoprotein of vesicular stomatitis virus (ts-O45-G) from the ER to the cell surface in intact Vero cells. While COPII dependent export of ts-O45-G from the ER is blocked in cells injected with recombinant p...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::The establishment of the junctional complex in epithelial cells requires the presence of extracellular calcium, and is controlled by a network of reactions involving G-proteins, phospholipase C and protein kinase C. Since potential candidates for phosphorylation are the tight junction associated proteins ZO1, ZO2 and ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::Ca(2+) signaling mediated by phospholipase C that produces inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] and diacylglycerol (DAG) controls lymphocyte activation. In contrast to store-operated Ca(2+) entry activated by Ins(1,4,5)P(3)-induced Ca(2+) release from endoplasmic reticulum, the importance of DAG-activated Ca(...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.061051
更新日期:2010-03-15 00:00:00
abstract::We use the fungus Ashbya gossypii to investigate how its polar growth machinery is organized to achieve sustained hyphal growth. In slowly elongating hyphae exocyst, cell polarity and polarisome proteins permanently localize as cortical cap at hyphal tips, thus defining the zone of secretory vesicle fusion. In tenfold...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.033852
更新日期:2008-12-01 00:00:00
abstract::In hepatocytes, PLIN2 is the major protein coating lipid droplets (LDs), an organelle the hepatitis C virus (HCV) hijacks for virion morphogenesis. We investigated the consequences of PLIN2 deficiency on LDs and on HCV infection. Knockdown of PLIN2 did not affect LD homeostasis, likely due to compensation by PLIN3, bu...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.217042
更新日期:2019-01-09 00:00:00
abstract::Microscopic green algae inhabiting desert microbiotic crusts are remarkably diverse phylogenetically, and many desert lineages have independently evolved from aquatic ancestors. Here we worked with five desert and aquatic species within the family Scenedesmaceae to examine mechanisms that underlie desiccation toleranc...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.212233
更新日期:2018-04-10 00:00:00
abstract::Alix is a cytosolic protein in mammalian cells that was originally identified on the basis of its association with pro-apoptotic signaling. More recent evidence has established that Alix has a hand in regulating other cellular mechanisms, including endocytic membrane trafficking and cell adhesion. Although Alix appear...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.03072
更新日期:2006-08-01 00:00:00
abstract::Cutaneous wound healing is accelerated by exogenous mechanical forces and is impaired in TRPC6-knockout mice. Therefore, we designed experiments to determine how mechanical force and TRPC6 channels contribute to wound healing using HaCaT keratinocytes. HaCaT cells were pretreated with hyperforin, a major component of ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.147314
更新日期:2014-10-01 00:00:00
abstract::The molecular chaperone Hsp90 has been found ubiquitously as a predominantly cytoplasmic dimer. By interacting with cytoplasmic or nuclear proteins such as pp60v-src or steroid receptors, Hsp90 helps its targets to become competent for full biological activity. Mutational deletion analysis of some properties of chicke...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::Inositol-(1,4,5)-triphosphate receptors (InsP(3)Rs) are ligand-gated Ca(2+) channels that control Ca(2+) release from intracellular stores and play a central role in a wide range of cellular responses. In most epithelial cells, InsP(3)Rs are not uniformly distributed within the endoplasmic reticulum (ER) membrane, wit...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.108738
更新日期:2012-11-15 00:00:00
abstract::Elementary Ca(2+) signals, such as "Ca(2+) puffs", which arise from the activation of inositol 1,4,5-trisphosphate receptors, are building blocks for local and global Ca(2+) signalling. We characterized Ca(2+) puffs in six cell types that expressed differing ratios of the three inositol 1,4,5-trisphosphate receptor is...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract::Pex11 homologs and dynamin-related proteins uniquely regulate peroxisome division (cell-cycle-dependent duplication) and proliferation (cell-cycle-independent multiplication). Arabidopsis plants possess five Pex11 homologs designated in this study as AtPex11a, -b, -c, -d and -e. Transcripts for four isoforms were foun...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02904
更新日期:2006-05-01 00:00:00
abstract::To clarify the involvement of actin in the formation of the yeast cell wall, reverting protoplasts of Schizosaccharomyces pombe were used as a simple model system. Actin of reverting protoplasts was labeled with rhodamine-conjugated phalloidin and observed by conventional fluorescence microscopy and laser scanning con...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::We have shown previously, by fluorescent antibody staining, that desmosomal antigens are widely distributed in the tissues of vertebrate animals. Furthermore, we have demonstrated mutual desmosome formation between cells derived from man, cow, dog, chicken and frog. In this paper we have studied the components of desm...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00