Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A key problem in nervous system development is how distinct subpopulations of progenitor cells give rise to different adult brain structures. The labeling pattern of the FORSE-1 antibody subdivides the neuroepithelium of the embryonic forebrain into domains resembling those of certain transcription factors, suggesting that the FORSE-1 epitope may be involved in the specification of development compartments. Therefore, it is important to determine the identity of the antigen(s) recognized by FORSE-1. On immunoblots, FORSE-1 recognizes a single, high-molecular-weight species, which we have identified as phosphacan, a brain-specific chondroitin sulfate proteoglycan that binds neural cell adhesion molecules. This identification is based on cross-immunoprecipitations and immunoblotting using an anti-phosphacan antibody and FORSE-1. FORSE-1 also recognizes two major neutral glycolipids in embryonic brain. The FORSE-1 epitope is sensitive to endo-beta-galactosidase, suggesting that the epitope corresponds to a carbohydrate moiety. Moreover, immunoprecipitates of the proteoglycan bearing the FORSE-1 epitope bind antibodies that recognize the Le* carbohydrate, and immunostaining patterns of embryonic brain sections by FORSE-1 and a known anti-Le* antibody are identical. Finally, purified FORSE-1 specifically recognizes Le*-containing glycoconjugates in ELISAs. The pattern of FORSE-1 labeling, the identification of its epitope as Le*, which has implicated in cell adhesion, and the presence of Le* on phosphacan suggest that this carbohydrate epitope may play a role in adhesive interactions important for proliferation, cell migration, or axon guidance.
Mol Cell Neurosci 1995 Aug
PMID:FORSE-1, an antibody that labels regionally restricted subpopulations of progenitor cells in the embryonic central nervous system, recognizes the Le(x) carbohydrate on a proteoglycan and two glycolipid antigens. 884 6

Tumor cell invasion of basement membranes (BM) represents one of the critical steps in the metastatic process. Tumor cell recognition of individual BM matrix components may involve individual cell adhesion receptors, such as integrins or cell surface proteoglycans, or may involve a coordinate action of both types of receptors. In this study, we have focused on the identification of a cell surface CD44/chondroitin sulfate proteoglycan (CSPG) and alpha 2 beta 1 integrin on human melanoma cells that are both directly involved in the in vitro invasion of reconstituted BM via a type IV collagen-dependent mechanism. Interfering with cell surface expression of human melanoma CSPG with either p-nitro-phenyl-beta-D-xylopyranoside treatment or anti-CD44 monoclonal antibody (mAb) preincubation (mAb) preincubation inhibits melanoma cell invasion through reconstituted BM. These treatments also strongly inhibit melanoma cell migration on type IV collagen, however, they are ineffective at inhibiting cell adhesion to type IV collagen. Purified melanoma cell surface CD44/CSPG, or purified chondroitin sulfate, bind to type IV collagen affinity columns, consistent with a role for CD44/CSPG-type IV collagen interactions in mediating tumor cell invasion. In contrast, melanoma cell migration on laminin (LM) does not involve CD44/CSPG, nor does CD44/CSPG bind to LM, suggesting that CD44/CSPG-type IV collagen interactions are specific in nature. Additionally, anti-alpha 2 and anti-beta 1 integrin mAbs are capable of blocking melanoma cell invasion of reconstituted BM. Both of these anti-integrin mAbs inhibit melanoma cell adhesion and migration on type IV collagen, whereas only anti-beta 1 mAb inhibits cell adhesion to LM. Collectively, these results indicate that melanoma cell adhesion to type IV collagen is an important consideration in invasion of reconstituted BM in vitro, and suggest that CD44/CSPG and alpha 2 beta 1 integrin may collaborate to promote human melanoma cell adhesion, migration, and invasion in vivo.
Mol Biol Cell 1996 Mar
PMID:CD44/chondroitin sulfate proteoglycan and alpha 2 beta 1 integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes. 886 67

The myocardial extracellular matrix (ECM) is composed of three important constituents: (1) fibrillar collagen, (2) a basement membrane, and (3) proteoglycans. Structural or compositional changes in these ECM components may affect left ventricular (LV) function as well as influence overall LV geometry. Accordingly, this study examined the relationship between changes in these ECM components to changes in LV function and geometry which develop with the progression and regression from supraventricular tachycardia-induced cardiomyopathy (SVT). LV function and specific components of the ECM were studied in pigs with SVT cardiomyopathy (SVT:atrially paced 240 bpm, 3 weeks; n = 7), or after a 4-week recovery from SVT cardiomyopathy (post-SVT; n = 6), and in controls (n = 7). LV fractional shortening fell by 60% and end-diastolic dimension increased by 47% with SVT compared to controls. While LV fractional shortening normalized with post-SVT, end-diastolic dimension remained 40% higher than controls. Collagen concentration fell by 22% and salt extractable collagen, which reflects collagen cross-linking, increased by 41% with SVT compared to controls. Collagen concentration increased by 20%, collagen extraction normalized, and levels of collagen type III mRNA increased by 42% with post-SVT. Isolated myocyte adhesion capacity to basement membrane substrates laminin, fibronectin, and collagen type IV were examined. SVT resulted in over a 50% reduction in myocyte adhesion for all of the basement membrane components compared to controls. A normalization in isolated myocyte adhesion capacity was observed in post-SVT. The relative content and distribution of the ECM proteoglycan chondroitin sulfate was examined using immunohistochemistry. With SVT, the density of this proteoglycan increased around individual myocytes. With post-SVT, the relative distribution of chondroitin sulfate returned to control levels. Thus, SVT cardiomyopathy was associated with reduced collagen concentration and cross-linking, diminished myocyte basement membrane adhesion capacity, and increased proteoglycans. Recovery from SVT cardiomyopathy resulted in increased collagen concentration, and a normalization of myocyte adhesion capacity and proteoglycan distribution. These results suggest that changes within the ECM are a dynamic process and accompany the LV systolic and diastolic function as well as ventricular and myocyte remodeling during the progression and regression from cardiomyopathic disease.
J Mol Cell Cardiol 1996 Aug
PMID:Cellular and extracellular remodeling with the development and recovery from tachycardia-induced cardiomyopathy: changes in fibrillar collagen, myocyte adhesion capacity and proteoglycans. 887 70

Astrocyte-conditioned medium (ACM) supports the survival of rat E15 neocortical neurons. Using a microtiter assay for neuronal survival, we demonstrated that part of the survival activity is associated with a proteoglycan fraction obtained after two chromatographic steps: (1) preparative Q-Sepharose anion-exchange chromatography under non-denaturating conditions and (2) MonoQ chromatography in the presence of 8 M urea. Analytical SDS-polyacrylamide gradient gel electrophoresis of pooled active MonoQ-fractions (MQ-pool) revealed a broad proteoglycan band migrating with an apparent M(r) in the range of 150-400 kDa. Digestion of the MQ-pool with chondroitin-ABC-lyase yielded a major core protein of 50 kDa. In Western blots the high molecular weight (150-400 kDa) material as well as the 50 kDa core protein band were immunoreactive to chicken polyclonal antibodies raised against purified biglycan from rat meningeal fibroblasts. Northern blot analysis of total RNA prepared from highly enriched astrocyte cultures revealed a single 2.9 kb biglycan transcript. By using in situ hybridization we demonstrated that essentially all cells in these cultures expressed biglycan mRNA. Furthermore, highly purified biglycan from bovine cartilage was shown to markedly enhance survival of rat neocortical neurons. In conclusion, we have shown that astrocytes synthesize and release the small chondroitin/dermatan sulfate proteoglycan (CS/DSPG) biglycan, a molecule that was found to support survival of neocortical neurons in vitro.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Cultured astrocytes express biglycan, a chondroitin/dermatan sulfate proteoglycan supporting the survival of neocortical neurons. 888 35

A large chondroitin sulfate proteoglycan (CSPG) identified in embryonic chick brain, and synthesized exclusively by neurons in a developmentally expressed pattern that coincides with migration and establishment of neuronal nuclei, reacts with a monoclonal antibody (S103L) developed against the cartilage-specific CSPG, aggrecan. The relationship of the brain and cartilage S103L CSPGs was established by chemical, biosynthetic and molecular analyses. Significant posttranslational differences (absence of keratan sulfate (KS), less CS, and different sulfation patterns) distinguish the brain S103L species from the cartilage S103L species. However, quantitative and qualitative Northern analysis, cassette RT-PCR and direct cloning and sequencing of the entire brain-specific S103L CSPG coding sequence, all indicate that the brain and cartilage core proteins are identical. Thus, although the S103L CSPG synthesized by chick brain and cartilage are the product of a single gene, they are clearly biochemically distinct and differentially expressed proteoglycan products, suggesting tissue specific roles for these proteoglycan homologs.
Brain Res Mol Brain Res 1996 Mar
PMID:S103L reactive chondroitin sulfate proteoglycan (aggrecan) mRNA expressed in developing chick brain and cartilage is encoded by a single gene. 896 52

The transmembrane proteoglycan NG2 is able to interact both with components of the extracellular matrix and with the actin cytoskeleton. An examination of the distribution of NG2 during cell spreading suggests that NG2 can associate with two distinct types of actin-containing cytoskeletal structures, depending on the nature of the stimulus derived from the substratum. On fibronectin-coated dishes, cell surface NG2 associates exclusively with stress fibers developing within the cell. On poly-L-lysine-coated dishes, cell surface NG2 is associated with radial processes extending from the cell periphery. Spreading on fibronectin/poly-L-lysine mixtures, as well as on matrix components such as laminin, tenascin, and type VI collagen, produces cells with mosaic characteristics, i.e., NG2 is associated with both types of structures. NG2-positive radial processes are distinct from a second population of radial structures that contain fascin. NG2-positive extensions appear to be individual self-contained units (filopodia), whereas fascin is associated with actin ribs within sheets of membrane (lamellipodia). NG2- and fascin-positive structures are often localized to opposite poles of spreading cells, suggesting a possible role for the two classes of cellular extensions in the establishment of cell polarity during morphogenesis or migration. Time lapse imaging confirms the presence of lamellipodia on the leading edges of migrating cells, while numerous filopodia are present on trailing edges.
Mol Biol Cell 1996 Dec
PMID:NG2 proteoglycan and the actin-binding protein fascin define separate populations of actin-containing filopodia and lamellipodia during cell spreading and migration. 897 Jan 59

Primary cultures of rat hepatocytes maintained on different matrix proteins such as collagen (Co IV) fibronectin (Fn), Laminin (Ln) or different tissue biomatrices were metabolically labelled with 35[S]-SO4 and the synthesis of sulphated proteoglycans was studied. The incorporation of the label into total glycosaminoglycan (GAG) was significantly higher in cells maintained on Co IV compared to those maintained on Fn or Ln. Similarly the incorporation of label was maximum in those cells maintained on the aortic biomatrix compared to liver or mammary gland biomatrix. About 80-95% of the GAG synthesised and secreted by cells maintained on individual matrix proteins and liver biomatrix was heparan sulphate (HS). But in the case of cells maintained on collagen IV aortic or mammary biomatrix in addition to HS, significant amount of chondroitin sulphate (CS) was also found. Nearly 50% of the total 35[S]-GAG was associated with the cell layer after 24 h in culture in the case of cells maintained on individual matrix protein while those maintained on tissue biomatrix, retained about 70% of the 35[S]-labelled proteoglycans (PG) with the cell layer. Analysis of the cell surface 35[S]-labelled proteoglycans isolated from cells maintained on different biomatrix showed that it is a hybrid proteoglycan consisting of CS and HS. While the PG isolated from cells maintained on liver biomatrix consists of HS and CS in the ratio of 3:2 that from cells maintained on aorta or mammary gland matrix was about 2:3 indicating an alteration in the nature of the cell surface PGs produced by cells maintained on different tissue biomatrix. These results indicate that depending on the nature of the matrix substratum with which the cells are in contact, the nature and quantity of sulphated proteoglycans produced by hepatocytes vary.
Mol Cell Biochem 1996 Dec 06
PMID:Synthesis of sulphated proteoglycans by primary cultures of rat hepatocytes--modulation by matrix substratum. 897 75

Colony-stimulating factor-1 (CSF-1), also known as macrophage colony-stimulating factor, controls the survival, proliferation, and differentiation of mononuclear phagocytes and regulates cells of the females reproductive tract. It appears to play an autocrine and/or paracrine role in cancers of the ovary, endometrium, breast, and myeloid and lymphoid tissues. Through alternative mRNA splicing and differential post-translational proteolytic processing, CSF-1 can either be secreted into the circulation as a glycoprotein or chondroitin sulfate-containing proteoglycan or be expressed as a membrane-spanning glycoprotein on the surface of CSF-1-producing cells. Studies with the op/op mouse, which possesses an inactivating mutation in the CSF-1 gene, have established the central role of CSF-1 in directly regulating osteoclastogenesis and macrophage production. CSF-1 appears to preferentially regulate the development of macrophages found in tissues undergoing active morphogenesis and/or tissue remodeling. These CSF-1 dependent macrophages may, via putative trophic and/or scavenger functions, regulate characteristics such as dermal thickness, male fertility, and neural processing. Apart from its expression on mononuclear phagocytes and their precursors, CSF-1 receptor (CSF-1R) expression on certain nonmononuclear phagocytic cells in the female reproductive tract and studies in the op/op mouse indicate that CSF-1 plays important roles in female reproduction. Restoration of circulating CSF-1 to op/op mice has preliminarily defined target cell populations that are regulated either humorally or locally by the synthesis of cell-surface CSF-1 or by sequestration of the CSF-1 proteoglycan. The CSF-1R is a tyrosine kinase encoded by the c-fms proto-oncogene product. Studies by several groups have used cells expressing either the murine or human CSF-1R in fibroblasts to pinpoint the requirement of kinase activity and the importance of various receptor tyrosine phosphorylation sites for signaling pathways stimulated by CSF-1. To investigate post-CSF-1R signaling in the macrophage, proteins that are rapidly phosphorylated on tyrosine in response to CSF-1 have been identified, together with proteins associated with them. Studies on several of these proteins, including protein tyrosine phosphates 1C, the c-cbl proto-oncogene product, and protein tyrosine phosphatase-phi are discussed.
Mol Reprod Dev 1997 Jan
PMID:Biology and action of colony--stimulating factor-1. 898 57

There is a close interaction between the processes involved in osteogenesis and hemopoiesis. In developing bone, the osteoclasts, cells of hemopoietic origin, resorb and invade the calcified cartilage rudiment. As a result, the primitive marrow cavity is formed and hemopoiesis initiates. Osteogenic cells-osteoblasts and osteocytes-control the development and activity of the osteoclasts through the local release of factors. One factor responsible for this osteoblast-osteoclast interaction is colony-stimulating factor-1 (CSF-1). Studies performed on the osteopetrotic op/op mouse mutant have established that this factor is essential for proliferation and differentiation of the osteoclasts. Expression of CSF-1 receptors by mature osteoclasts and osteoclast precursors strongly suggests that CSF-1 action is exerted directly on cells of this lineage. In vivo, CSF-1 synthesis by osteoblasts is temporally and spatially related to sites of osteoclast development. Thus CSF-1 may represent one of the factors responsible for coupling hemopoiesis to osteogenesis. In vitro, osteoblasts express at least 4 transcripts encoding either a secreted or a membrane-bound form of CSF-1. At the protein level, osteoblasts in vitro synthesize the membrane-bound form and secrete the majority of CSF-1 as a proteoglycan, a small fraction of which is integrated into the matrix. These different molecular forms may locally restrict the biological action of this cytokine. Indeed, injection of recombinant human CSF-1 in op/ op mutants does not correct the osteoclast deficiency in the metaphyseal spongiosa of long bones, and sclerosis persists at this site. Similarly, the deficiency of some tissue macrophage populations in op/op mice is only partially or not at all corrected by injection of CSF-1. The expression of CSF-1 receptors by mature osteoclasts may imply that CSF-1 also influences their bone resorbing activity. Indeed, CSF-1 has been shown to induce osteoclast fusion, spreading, and survival. These findings suggest that CSF-1 is essential for the proliferation, differentiation, activity, and survival of tissue macrophages and osteoclasts, cells involved in tissue turnover. Furthermore, they corroborate the view that both osteoclasts and tissue macrophages stem from a CSF-1-dependent common precursor along the macrophage lineage.
Mol Reprod Dev 1997 Jan
PMID:Role of CSF-1 in bone and bone marrow development. 898 67

The possible involvement of proteoglycans in the pathogenesis of emphysema was studied in rats by a single intratracheal instillation of p-nitrophenyl-beta-D-xylopyranoside (beta-D-xyloside), an inhibitor of proteoglycan synthesis. The first 3 days after instillation are characterized by mild hemorrhages, some infiltration of inflammatory cells, and edema. After 1 wk, lung morphology is normal again. Forty days after instillation, considerable parenchymal destruction has occurred as determined by the mean linear intercept (81 +/- 12 microns versus 57 +/- 5 microns for control [P < 0.001]). Pulmonary fibrosis is not observed. Instillation with p-nitrophenyl-alpha-D-xylopyranoside and p-nitrophenol do not induce parenchymal destruction, indicating the specificity of beta-D-xyloside action. Urinary glycosaminoglycan (GAG) content of the beta-D-xyloside-treated rats is increased 15-fold during the first day after instillation, mainly due to elevated levels of chondroitin sulfate and dermatan sulfate. The increase is correlated to the extent of parenchymal destruction after 40 days (r = 0.68; P < 0.002). At day 2 and thereafter, levels are normal again. A short-term increase in dermatan and chondroitin sulfate content is also observed in serum, bronchoalveolar lavage (BAL) fluid, and lung tissue. Heparan sulfate content is decreased in BAL fluid and lung tissue. Instillation with p-nitrophenyl-alpha-D-xylopyranoside and p-nitrophenol do not induce elevated GAG concentration in urine. We suggest that a disturbance in proteoglycan synthesis accompanied by an increase of (beta-D-xyloside-primed) free GAGs results in loss of stability and integrity of the alveolar wall, leading to parenchymal destruction and emphysematous lesions. beta-D-xyloside treatment may be an alternative experimental method for inducing emphysema.
Am J Respir Cell Mol Biol 1997 Jan
PMID:Induction of emphysematous lesions in rat lung by beta-D-xyloside, an inhibitor of proteoglycan synthesis. 899 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>