6 research outputs found
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Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling
Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of alpha 2 beta 1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, alpha 2E336A, in the alpha 2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling
Recommended from our members
Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling
Intracellular Degradation of Multilabeled Poly(Ethylene imine)–Mesoporous Silica–Silica Nanoparticles: Implications for Drug Release
Mesoporous
silica nanoparticles, MSNs, have emerged as an interesting
carrier for drugs <i>in vitro</i> and <i>in vivo.</i> The particles are typically used in a surface functionalized form,
where functional silanes or other covalently linked surface functions
are used to provide anchoring sites for additional functionalities
like targeting groups, imaging agents, and drugs. Here, we report
results related to extra- and intracellular degradation of silica
nanoparticles using multilabeled nonporous silica core–mesoporous
silica shell–surface hyperbranched
poly(ethylene imine) shell nanoparticles as model particles. Different
fluorophores have been selectively covalently linked to different
regions of the particles in order to study the particle degradation
in detail under <i>in vitro</i> conditions in human SAOS-2
cells. A novel, quantitative method for nanoparticle degradation evaluation
based on confocal fluorescence microscopy is applied. Our results
suggest that the core–shell–shell MSNs degrade at a
higher rate inside cells as compared to outside
cells, which is of high importance for further application of this
class of drug carriers