Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanisms of myelin formation/reformation in the central nervous system are unknown. In previous work we have demonstrated that mature oligodendrocytes (OLG) respond to a signal(s), elicited by their adhesion to a substratum, by turning on a myelinogenic metabolism. Events occurring within 24 hr of adhesion include generation of diacylglycerol, activation of protein kinase C, phosphorylation of myelin basic protein, and enhanced synthesis of myelin lipids and proteins. To elucidate the mechanism(s) of signal transduction, we have investigated whether OLG-substratum interaction influences the level of basal cAMP and the expression of receptors coupled to adenylate cyclase. By using ovine brain OLG we have found that adhesion to a polylysine-coated surface for 24 hr increased the basal level of cAMP 2-fold and altered the expression (assessed by cAMP production) of receptors coupled to adenylate cyclase. Isoproterenol (beta-adrenergic agonist) augmented cAMP from 4 to 26 pmol/mg of protein in adhering OLG but had no such effect in nonattached OLG. Adhesion of OLG was accompanied by rapid synthesis of ethanolamine plasmalogen, a class of lipids believed to be associated with beta-adrenergic receptors. Nonattached OLG responded to prostaglandin E1 with only a 3-fold stimulation in their cAMP content; in attached OLG, 6-fold stimulation was observed. In contrast, vasoactive intestinal polypeptide elicited a 3-fold increase in cAMP in nonattached OLG but, following 24 hr of attachment, OLG did not respond to vasoactive intestinal polypeptide. The increase of cellular cAMP levels was accompanied by a 2.5-fold gain in protein kinase A. OLG-substratum adhesion resulted also in phosphorylation of the OLG/myelin protein, 2',3'-cyclic nucleotide 2'-phosphodiesterase, which proved to be a substrate for cAMP and phospholipid-, Ca2+-dependent protein kinases. These findings, in conjunction with our earlier work, implicate cAMP and diacylglycerol in signaling myelinogenesis; they suggest that phosphorylation/dephosphorylation of myelin basic protein and 2',3'-cyclic nucleotide 2'-phosphodiesterase may be key processes in the cascade of events that are initiated by adhesion of OLG to a polylysine surface (possibly acting as a surrogate for axons) and culminate in the reformation of myelin.
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PMID:Oligodendrocyte substratum adhesion modulates expression of adenylate cyclase-linked receptors. 244 85

Cell-substratum adhesion plays a crucial part in the cascade of events that control growth or turn on and consummate a differentiation program. We are investigating the molecular basis of oligodendrocyte (OLG) cytodifferentiation, employing pure cultures of OLGs isolated from postmyelination brains. We have shown that such OLGs will regenerate in vitro and reenact the ontogenic development of myelin, but to do so they need a signal. Adherence to a polylysine surface in the presence of 20% horse serum generates such a signal. Among the events that are turned on upon OLG adhesion is the phosphorylation of myelin basic protein; no such phosphorylation takes place in the non-adhered cell. We postulated that horse serum provides an adhesion molecule. Laminin, fibronectin, collagen and native vitronectin failed to replace horse serum. Hence, we set out to fractionate horse serum by screening with an adhesion assay. We report here the identification, purification and partial characterization of a novel, heparin-binding horse serum glycoprotein that we have termed Glycine-Rich Adhesion Serum Protein--GRASP--to stress the fact that this protein has a high content of glycine and functions, in vitro, as an adhesion molecule for OLGs. There is 61% similarity at the N-terminus between GRASP and histidine-rich glycoprotein precursor (HRGP), an alpha 2-glycoprotein from human plasma. However, our data suggest that GRASP is not the horse serum homolog of HRGP. First, the two Gps are functionally distinct: HRGP does not promote the adhesion of OLGs. Second, the amino acid compositions differ significantly, e.g., GRASP is not histidine- but rather glycine-rich. Third, the region of sequence similarity between GRASP and HRGP is conserved throughout the cystatin superfamily. Fourth, anti-Gp55 polyclonal Abs recognize a similar set of polypeptides--save for slight differences in M(r)-in human serum as in horse serum, indicating that HRGP and GRASP are two distinct but related proteins and are both present in human and horse sera. GRASP is a dimer trimer of seemingly identical subunits of M(r) approximately 55,000 ; the native protein has an M(r) x 10(-3) approximately 120-140, of which 24-27% is contributed by carbohydrate. Using GRASP as a substratum allows the growth of OLGs in serum-free medium. GRASP is as good an effector of myelin basic protein phosphorylation as 20% horse serum. We conjecture that the mechanism of GRASP function features: 1) exposure of a cryptic sequence--after a change in conformation induced upon binding to polylysine--with affinity for an OLG signal-transducing receptor; and 2) interaction of its heparin-binding domain with OLG surface heparin sulfate proteoglycans and/or the aforementioned receptor.
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PMID:GRASP: a novel heparin-binding serum glycoprotein that mediates oligodendrocyte-substratum adhesion. 753 46

Adhesion to extracellular matrix mediates cell cycle progression in mid-late G1; this effect involves an integrin-dependent organization of the cytoskeleton and a consequent change in cell shape. In an effort to identify potential signal-transducing agents that are associated with integrin-dependent shape changes, we looked for kinase activities that were stimulated by long-term adhesion of G0-synchronized NIH-3T3 cells to fibronectin-coated dishes. Several kinase activities were stimulated by this procedure, two of which migrated at 42 and 44 kDa and phosphorylated myelin basic protein in vitro. Blotting with anti-phosphotyrosine and anti-mitogen-activated protein (MAP) kinase antibodies identified these enzymes as ERK 1 and ERK 2. In contrast to the rapid and transient activation of these MAP kinases by platelet-derived growth factor, stimulation of MAP kinase activity by fibronectin was gradual, persistent, and associated with cell spreading rather than cell attachment itself. Cytochalasin D blocked the activation of MAP kinase activity that was induced by the binding of cells to fibronectin. Moreover, MAP kinase was also activated by adhesion of cells to vitronectin and type IV collagen; these effects were also associated with cell spreading. These results distinguish the regulation of G1 phase MAP kinase activity by soluble mitogens and extracellular matrix. They also implicate MAP kinase in shape-dependent cell cycle progression.
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PMID:Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation. 761 63

Adhesion molecules probably are required for the migration of T lymphocytes to inflamed tissues, but the roles of these molecules have yet to be understood in the pathogenesis of inflammatory diseases such as multiple sclerosis. The adhesion of an SJL murine T cell clone specific for myelin basic protein (MBP) to endothelial cells (ECs) from SJL newborn brain microvessels was examined. Sixty percent of the 2 x 10(4) T cell clones stimulated once every 2 weeks with MBP were bound to ECs, whereas less than 5% of the same number of lymphocytes from peripheral lymph nodes were bound. However, binding was not central nervous system (CNS)-specific. Monoclonal antibody to VLA-4 or VCAM-1 partially inhibited the binding of the T cell clone to ECs. Binding of the T cell clone to ECs increased when the latter were incubated with IL-1 or TNF, but was not inhibited by anti-VLA-4 or VCAM-1. We suggest that the VLA-4/VCAM-1 pathway functions in the binding of the T cell clone specific for MBP to brain ECs but that adhesion molecules other than VLA-4/VCAM-1 are involved because anti-VLA-4 and anti-VCAM-1 did not produce complete inhibition.
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PMID:Binding of an SJL T cell clone specific for myelin basic protein to SJL brain microvessel endothelial cells is inhibited by anti-VLA-4 or its ligand, anti-vascular cell adhesion molecule 1 antibody. 768 92

Adhesive interactions between murine cerebrovascular endothelial cells (EC) which comprise the blood-brain barrier (BBB) and myelin basic protein (MBP)-specific encephalitogenic T lymphocytes were investigated. Adhesion was assessed by measuring the percent attachment of 51Cr-labeled T cells to EC monolayers. The basal level adhesion (20-35%) was significantly up-regulated by treating EC with recombinant murine gamma interferon (IFN-gamma), interleukin-1 alpha (IL-1 alpha) and/or tumor necrosis factor-alpha (TNF alpha). The ability of these cytokines to modulate adhesion was dose- and time-dependent and could be detected as early as 1 h after treatment. The expression of intercellular adhesion molecule-1 (ICAM-1) by EC was examined by immunofluorescence staining and ELISA. Although all unstimulated EC cultures expressed ICAM-1, treatment of EC with the above cytokines dramatically up-regulated the level of ICAM-1 expression in a dose- and time-dependent fashion similar to that observed in the adhesion assays. Treatment of EC with transforming growth factor-beta 1 (TGF beta) down-regulated the level of T cell adhesion on untreated EC in a dose-dependent manner. Pretreatment of EC with TGF beta also partially inhibited the up-regulation of adhesion induced by IFN-gamma, IL-1 alpha and/or TNF alpha. TGF beta had no effect on the up-regulation of ICAM-1 expression induced by IFN-gamma, IL-1 alpha and/or TNF alpha. These results indicate that in addition to ICAM-1, other molecules may be involved in adhesion of encephalitogenic T cells to the EC comprising the cerebral vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine-regulated adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells. 809 22

Adhesion molecules are believed to facilitate infiltration of leukocytes into the CNS of mice with experimental allergic encephalomyelitis (EAE). The role of the adhesion molecule CD62L (L-selectin) in the immunopathology of EAE is not known. To study this, we crossed CD62L-deficient mice with myelin basic protein-specific TCR (MBP-TCR) transgenic mice. CD62L-deficient MBP-TCR transgenic mice failed to develop antigen-induced EAE, and, despite the presence of leukocyte infiltration, damage to myelin in the CNS was not seen. EAE could, however, be induced in CD62L-deficient mice upon adoptive transfer of wild-type macrophages. Our results suggest that CD62L is not required for activation of autoimmune CD4 T cells but is important for the final destructive function of effector cells in the CNS and support a novel mechanism whereby CD62L expressed on effector cells is important in mediating myelin damage.
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PMID:CD62L is required on effector cells for local interactions in the CNS to cause myelin damage in experimental allergic encephalomyelitis. 1129 Mar 38

Oligodendrocyte progenitor cells first proliferate to generate sufficient cell numbers and then differentiate into myelin-producing oligodendrocytes. The signal transduction mediators that underlie these events, however, remain poorly understood. The tyrosine phosphatase Shp1 has been linked to oligodendrocyte differentiation as Shp1-deficient mice show hypomyelination. The Shp1 homolog, Shp2, has recently been shown to regulate astrogliogenesis, but its role in oligodendrocyte development remains unknown. Here, we report that Shp2 protein levels were developmentally regulated in oligodendrocytes, with Shp2 phosphorylation being promoted by oligodendroglial mitogens but suppressed by laminin, an extracellular matrix protein that promotes oligodendroglial differentiation. In contrast, oligodendrocyte progenitors were found to be unresponsive to mitogens following Shp2, but not Shp1, depletion. In agreement with previous studies, Shp1 depletion led to decreased levels of myelin basic protein in differentiating oligodendrocytes, as well as reduced outgrowth of myelin membrane sheets. Shp2 depletion in contrast did not prevent oligodendrocyte differentiation but promoted expanded myelin membrane outgrowth. Taken together these data suggest that Shp1 and Shp2 have distinct functions in oligodendrocyte development: Shp2 regulates oligodendrocyte progenitor proliferation and Shp1 regulates oligodendrocyte differentiation. Adhesion to laminin may additionally provide extrinsic regulation of Shp2 activity and thus promote the transition from progenitor to differentiating oligodendrocyte.
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PMID:Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in oligodendrocyte development. 2013 81