Search results for "binding"
showing 10 items of 3896 documents
Integrin alpha(2)I domain recognizes type I and type IV collagens by different mechanisms.
2000
The collagens are recognized by the alphaI domains of the collagen receptor integrins. A common structural feature in the collagen-binding alphaI domains is the presence of an extra helix, named helix alphaC. However, its participation in collagen binding has not been shown. Here, we have deleted the helix alphaC in the alpha(2)I domain and tested the function of the resultant recombinant protein (DeltaalphaCalpha(2)I) by using a real-time biosensor. The DeltaalphaCalpha(2)I domain had reduced affinity for type I collagen (430 +/- 90 nM) when compared with wild-type alpha(2)I domain (90 +/- 30 nM), indicating both the importance of helix alphaC in type I collagen binding and that the collag…
α5β1 integrin-mediated adhesion to fibronectin is required for axis elongation and somitogenesis in mice.
2011
The arginine-glycine-aspartate (RGD) motif in fibronectin (FN) represents the major binding site for α5β1 and αvβ3 integrins. Mice lacking a functional RGD motif in FN (FN(RGE/RGE)) or α5 integrin develop identical phenotypes characterized by embryonic lethality and a severely shortened posterior trunk with kinked neural tubes. Here we show that the FN(RGE/RGE) embryos arrest both segmentation and axis elongation. The arrest is evident at about E9.0, corresponding to a stage when gastrulation ceases and the tail bud-derived presomitic mesoderm (PSM) induces α5 integrin expression and assumes axis elongation. At this stage cells of the posterior part of the PSM in wild type embryos are tight…
Cholesterol Dependence of Collagen and Echovirus 1 Trafficking along the Novel α2β1 Integrin Internalization Pathway
2013
We have previously shown that soluble collagen and a human pathogen, echovirus 1 (EV1) cluster α2β1 integrin on the plasma membrane and cause their internalization into cytoplasmic endosomes. Here we show that cholesterol plays a major role not only in the uptake of α2β1 integrin and its ligands but also in the formation of α2 integrin-specific multivesicular bodies (α2-MVBs) and virus infection. EV1 infection and α2β1 integrin internalization were totally halted by low amounts of the cholesterol-aggregating drugs filipin or nystatin. Inhibition of cholesterol synthesis and accumulation of lanosterol after ketoconazole treatment inhibited uptake of collagen, virus and clustered integrin, an…
The Selective Regulation of αVβ1 Integrin Expression Is Based on the Hierarchical Formation of αV-containing Heterodimers
2002
The integrin beta1 subunit can form a heterodimer with 12 different alpha subunits. According to the present model, the expression level of any alphabeta complex is regulated by the availability of the specific alpha subunit, whereas beta1 subunit is constantly present in a large excess. The expression of several heterodimers containing the alphaV subunit seems to be regulated by an identical mechanism. The fact that many cells express alphaVbeta1 heterodimer, and that this fibronectin/vitronectin receptor may be selectively regulated, compromises the present model of the regulation of beta1 and alphaV integrins. We have tried to solve this problem by assuming that distinct alphabeta hetero…
Integrin alpha 2 beta 1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3 beta.
2002
The integrins are a large family of heterodimeric transmembrane receptors composed of α and β subunits (22). In addition to mediating cell-matrix interactions, integrins have been shown to activate intracellular signaling pathways which, in collaboration with growth factor-induced signals, regulate cellular functions (46). Some integrin signaling cascades are activated via the β subunit cytoplasmic domain, and they are therefore triggered by several integrin heterodimers. These signals include the activation of protein tyrosine kinases of the Src and focal adhesion kinase (FAK) families (9, 47). More-recent studies have revealed signaling events that are activated specifically by an α subun…
The collagen receptor subfamily of the integrins
2003
The four collagen receptor integrins, alpha1beta1, alpha2beta1, alpha10beta1 and alpha11beta1, form a structurally and functionally distinct subgroup when compared to other members of the integrin family. In this review, we discuss the structures of these receptors and their differences in collagen binding and signalling function.
The Dorsocross T-box transcription factors promote tissue morphogenesis in the Drosophila wing imaginal disc.
2012
The Drosophila wing imaginal disc is subdivided into notum, hinge and blade territories during the third larval instar by formation of several deep apical folds. The molecular mechanisms of these subdivisions and the subsequent initiation of morphogenic processes during metamorphosis are poorly understood. Here, we demonstrate that the Dorsocross (Doc) T-box genes promote the progression of epithelial folds that not only separate the hinge and blade regions of the wing disc but also contribute to metamorphic development by changing cell shapes and bending the wing disc. We found that Doc expression was restricted by two inhibitors, Vestigial and Homothorax, leading to two narrow Doc stripes…
Induction of interferon regulatory factors, 2′‐5′ oligoadenylate synthetase, P68 kinase and RNase L in chronic myelogenous leukaemia cells and its re…
1996
The genes crucially determining the therapeutic response of chronic myelogenous leukaemia (CML) to interferon-alpha (IFN-alpha) are unknown. Recently, two independent IFN-alpha signalling pathways were identified: the classic pathway mediates induction of 2'-5' oligoadenylate synthetase (2-5 OAS), p68 kinase and IFN regulatory factor-2 (IRF-2), whereas the alternate pathway leads to activation of IFN regulatory factor-1 (IRF-1). We investigated whether deficient or imbalanced expression of components of these two pathways is associated with resistance of CML cells to antiproliferative action of IFN alpha/beta. Constitutive and IFN-induced transcript levels of IFN-dependent genes in mononucl…
Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase.
2001
AbstractThe bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage-dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment. In contrast to what is observed with other DNA damaging agents, we demonstrate that the activation of CHK2 can only take place during S-phase. Use of wortmannin and caffeine suggests that this effect is no…
Docosahexaenoic Acid Induces Increases in [Ca2+]ivia Inositol 1,4,5-Triphosphate Production and Activates Protein Kinase Cγ and -δ via Phosphatidylse…
2007
We investigated, in monocytic leukemia U937 cells, the effects of docosahexaenoic acid (DHA; 22:6 n-3) on calcium signaling and determined the implication of phospholipase C (PLC) and protein kinase C (PKC) in this pathway. DHA induced dose-dependent increases in [Ca2+]i, which were contributed by intracellular pool, via the production of inositol-1,4,5-triphosphate (IP3) and store-operated Ca2+ (SOC) influx, via opening of Ca2+ release-activated Ca2+ (CRAC) channels. Chemical inhibition of PLC, PKCgamma, and PKCdelta, but not of PKCbeta I/II, PKCalpha, or PKCbetaI, significantly diminished DHA-induced increases in [Ca2+]i. In vitro PKC assays revealed that DHA induced a approximately 2-fol…