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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bacterial endotoxin LPS is a potent stimulator of monocyte and macrophage activation and induces adhesion of monocytes. Morphological changes in response to LPS have not been characterized in detail, however, nor have the signaling pathways mediating LPS-induced adhesion been elucidated. We have found that LPS rapidly induced adhesion and spreading of peripheral blood monocytes, and that this was inhibited by the Src family kinase inhibitor PP1 and the phosphatidylinositide 3-kinase inhibitor LY294002. LPS also stimulated actin reorganization, leading to the formation of filopodia, lamellipodia, and membrane ruffles in Bac1 mouse macrophages. Proline-rich tyrosine kinase 2 (Pyk2), a tyrosine kinase related to focal adhesion kinase, and paxillin, a cytoskeletal protein that interacts with Pyk2, were both tyrosine phosphorylated in response to LPS in monocytes and macrophages. Both tyrosine phosphorylation events were inhibited by PP1 and LY294002. Adhesion also stimulated tyrosine phosphorylation of Pyk2 and paxillin in monocytes, and this was further enhanced by LPS. Finally, Pyk2 and paxillin colocalized within membrane ruffles in LPS-stimulated cells. These results indicate that LPS stimulation of monocytes and macrophages results in rapid morphological changes and suggest that Pyk2 and/or paxillin play a role in this response.
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PMID:Lipopolysaccharide induces actin reorganization and tyrosine phosphorylation of Pyk2 and paxillin in monocytes and macrophages. 1065 55

Collagen stimulates platelet activation through a tyrosine kinase-based pathway downstream of the glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex. Genetic ablation of FcR gamma-chain results in a complete inhibition of aggregation to collagen. In contrast, a steady increase in light transmission is induced by collagen in phospholipase Cgamma2-deficient (PLCgamma2-/-) platelets in a Born aggregometer, indicating a weak level of activation. This increase is inhibited partially in the presence of an alpha2beta1-blocking antibody or an alphaIIbbeta3 antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibitor PP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (CRP) also stimulate weak aggregation in PLCgamma2-/- platelets, which is inhibited by wortmannin and PP1. Collagen and CRP stimulate tyrosine phosphorylation of PLCgamma1 at its regulatory site, Tyr 783, in murine but not in human platelets through a Src kinase-dependent pathway. Adhesion of PLCgamma2-/- platelets to a collagen monolayer is severely reduced at a shear rate of 800 s-1, relative to controls, whereas it is abolished in FcR gamma-chain-/- platelets. These results provide strong evidence that engagement of GPVI stimulates limited integrin activation in PLCgamma2-/- platelets via PLCgamma1 and PI3-kinase.
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PMID:Murine GPVI stimulates weak integrin activation in PLCgamma2-/- platelets: involvement of PLCgamma1 and PI3-kinase. 1273 Jan 18

Adhesions of cells to extracellular matrix and adjacent cells are mediated by integrins and VE-cadherin, respectively. Although these adhesion processes play crucial roles in vascular cell migration and angiogenesis, it remains unclear as to how they are coordinated to regulate cellular functions. We report here that integrin engagement by treating bovine endothelial aortic cell monolayers with beads coated with fibronectin (Fn) led to disruption of the VE-cadherin-containing adherens junctions. This disruption was accompanied by increases of tyrosine phosphorylation of beta-catenin, gamma-catenin, and p120ctn, as well as the dissociation of alpha-catenin and gamma-catenin from VE-cadherin. We applied a membrane-targeted Src reporter based on the fluorescence resonance energy transfer technique to visualize the dynamic Src activation at subcellular levels in live cells. The integrin engagement induced by Fn-coated beads caused the activation of Src around the beads and at adherens junctions, which are subsequently disrupted. The inhibition of Src with PP1 blocked the effects of integrin engagement on adherens junctions. Although Ras can also modulate adherens junctions, the resulting patterns of phosphorylation and association of junction proteins were distinct from those induced by integrin engagement. The inhibition of Ras by RasN17 did not rescue the disruption of adherens junctions induced by integrin engagement or by Src activation. Integrin engagement by Fn-coated beads also induced a significant alteration of cortical actin filaments at adherens junctions. The results indicate that integrin engagement disrupts VE-cadherin-containing adherens junctions via the activation of Src, but not Ras, possibly as a result of modulation of the actin network.
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PMID:Integrins regulate VE-cadherin and catenins: dependence of this regulation on Src, but not on Ras. 1644 27