Integrin β3 N125 glycosite was required for Mediating Human Cytomegalovirus Entry of Fibroblasts
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Luping Zheng
PROVIDER: PXD060540 | iProX | Thu Feb 06 00:00:00 GMT 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Invasion of leukocytes, including neutrophils, in response to injury or infection relies on the orchestrated activation of integrins. The neutrophil integrin lymphocyte function-associated antigen-1 (LFA-1) has been implicated in the regulation of leukocyte adhesion by binding to ICAM-1 expressed on activated endothelial cells. The activation-dependent conformational change of LFA-1 to the high affinity conformation (H+) requires kindlin-3 binding to the tail of the β2-integrin. How the integrin linked kinase (ILK) affects activation of β2-integrins in leukocytes is currently unknown. Here, utilizing in vitro microfluidic adhesion chambers with conformation specific antibodies for neutrophil-like HL-60 cells, we show that knockdown of ILK reduces the conformational change of β2-integrins to the H+ conformation. Consequently, ILK-deficient mice show defects of leukocyte adhesion and recruitment in a chemokine and integrin-dependent cremaster muscle model and in a clinically relevant model of renal-ischemia-reperfusion-injury. Absence of protein kinase C (PKC)-α, which is known to phosphorylate Kindlin-3, reproduces such phenotype in bone marrow chimeric mice. ILK is required for chemokine-induced upregulation of PKC-α activity. Mass spectrometry analysis and western blot analyses revealed a stimulation- and ILK-dependent phosphorylation of kindlin-3 upon activation. Our data thus show that ILK impacts kindlin-3-dependent conformational activation of LFA-1, thus contributing to an inflammatory response.
2020-07-20 | PXD017088 | Pride
Project description:Integrins are among the most abundant cell surface receptors constituting the principal adhesion receptors for the extracellular matrix (ECM), providing a physical anchor for the cell and triggering multiple intracellular signalling events. Loss-of function mutations of the integrin α3 gene (ITGA3) have been recently disclosed in patients with interstitial lung disease, congenital nephrotic syndrome and junctional epidermolysis bullosa, a multiorgan disorder with fatal outcome. In these patients, the respiratory function is strongly impaired and the kidneys are variably affected, whereas skin fragility is rather mild, has a delayed onset after birth or remains unrecognized, suggesting that integrin α3 differently influences the development and homeostasis of these organs. Here we employed authentic human keratinocytes bearing a naturally occurring integrin α3 loss-of-function mutation as a prototype to characterize the molecular mechanisms launched by the constitutional absence of this integrin subunit. To validate our findings, we generated new cellular models, including an additional ILNEB patient cell line, ITGA3 rescued and knockdown cells. We show that keratinocytes lacking a functional α3 subunit have an activated cellular phenotype with a switch in the pattern of integrin α subunits on the cell surface. These assure spreading and adhesion of epidermal keratinocytes but also drive the migratory phenotype of these cells.
2017-03-16 | GSE75838 | GEO
Project description:Geier2011 - Integrin activation
Rule based model that integrates the available data to test the biololical hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation.
This model is described in the article:
A computational analysis of the dynamic roles of talin, Dok1, and PIPKI for integrin activation.
Geier F, Fengos G, Iber D.
PLoS One. 2011;6(11):e24808.
Abstract:
Integrin signaling regulates cell migration and plays a pivotal role in developmental processes and cancer metastasis. Integrin signaling has been studied extensively and much data is available on pathway components and interactions. Yet the data is fragmented and an integrated model is missing. We use a rule-based modeling approach to integrate available data and test biological hypotheses regarding the role of talin, Dok1 and PIPKI in integrin activation. The detailed biochemical characterization of integrin signaling provides us with measured values for most of the kinetics parameters. However, measurements are not fully accurate and the cellular concentrations of signaling proteins are largely unknown and expected to vary substantially across different cellular conditions. By sampling model behaviors over the physiologically realistic parameter range we find that the model exhibits only two different qualitative behaviors and these depend mainly on the relative protein concentrations, which offers a powerful point of control to the cell. Our study highlights the necessity to characterize model behavior not for a single parameter optimum, but to identify parameter sets that characterize different signaling modes.
This model is hosted on BioModels Database
and identified
by: MODEL1208280001
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2014-03-05 | MODEL1208280001 | BioModels
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic reaction which includes an excess production of extracellular matrix and interacts with integrin adhesion receptors. Integrin adhesion complexes formed by HPDE cells (H6c7), with and without expression of mutant KRas G12V, were isolated and analysed by LC-MSMS
2022-05-20 | PXD027827 | Pride
Project description:The aim of these experiments was designed to compare gene expression in human myeloma cell lines expressing beta 3 integrin vs counterpart cell lines that do not express beta 3 integrin. Keywords: Gene expression,cell lines, siRNA
2009-04-29 | GSE15867 | GEO
Project description:Fibrosis is a pathological process characterized by persistent fibroblast activation and excessive extracellular matrix (ECM) accumulation. Aortic carboxypeptidase-like protein (ACLP), an ECM-associated protein that binds fibrillar collagen, is upregulated in fibrotic tissues and promotes fibroblast differentiation through canonical TGFβ receptor I signaling. We hypothesized that when presented within the collagen matrix, ACLP engages mechanically driven signaling pathway that contribute to fibroblast activation. Here, we identified a previously unrecognized mechanism through which collagen-bound ACLP activates fibroblasts via β1 integrin-mediated signaling. Collagen-bound ACLP induced rapid fibroblast spreading, increased β1 integrin activation, and promoted focal adhesion maturation. These early adhesion events were followed by elevated activation of the GTPases RhoA and Rac1, with enhanced F-actin assembly and nuclear accumulation of myocardin-related transcription factor A (MRTFA), a key regulator of activated fibroblast gene expression. Transcriptomic profiling revealed enrichment of focal adhesion, ECM–receptor interaction, and actin cytoskeletal gene pathways in response to collagen-bound ACLP. These findings establish collagen-bound ACLP as an ECM-derived cue that links matrix composition to fibroblast activation pathways.
2026-03-31 | GSE312027 | GEO
Project description:This series represents mature CD4+ lymphocytes with high and low expression of integrin α4β7 isolated from human subjects. Keywords = lymphocyte, integrin α4β7 , differential gene expression, microarray Keywords: parallel sample
2004-02-13 | GSE1039 | GEO
Project description:Aortic carboxypeptidase-like protein activates fibroblasts through β1 integrin signaling
| PRJNA1372083 | ENA
Project description:Cell states are governed by cell-intrinsic properties and external cues that regulate cell shape and signaling via cell-cell junctions or adhesions. Integrin β1-mediated adhesion is dispensable in early mouse embryogenesis at pre-implantation but becomes indispensable post-implantation. This implies distinct roles for β1-integrins in the naïve pre-implantation and primed post-implantation pluripotent stem cells (PSC). These, however, remain poorly understood. We investigated β1-integrin control of naïve-like and primed human induced PSC (hiPSC). We find that integrin β1 is active in naïve and primed hiPSCs and the degree of activity varies in vitro on different ECMs. Inhibition of integrin β1 in primed hiPSCs induces naïve-like colony features, reduces actomyosin contraction and ERK activity and alters gene expression, indicative of more naïve-like features. Integrin β1 inhibition supports epigenetic reversion of primed PSC to a naïve-like status, which involves dramatic reorganization of colony morphology, actin and adhesions. Furthermore, continued β1 integrin inhibition facilitates the maintenance of a naïve-like state through gene expression. These data reveal unprecedented integrin-dependent regulation of PSC states and demonstrate how integrin inhibitors may help to fine-tune hiPSC function and properties in vitro.
2025-06-03 | GSE205423 | GEO
Project description:Analysis of C2C12 myoblast induced with tetracycline to enhance integrin alpha7 expression. Integrin alpha7 is the major laminin binding integrin in muscle cells. Enhancing its expression has been demonstrated to alleviate pathology in a murine model of Duchenne muscular dystrophy. Results of this study provide insights into the effects of increasing integirn alpha7 expression on muscle cells and possible side effects associate with enhancing integrin alpha7 in muscle cells. Keywords: comparitive of integrin lapha7 induced and non-induced c2C12 myobalst
2007-12-23 | GSE8312 | GEO