Disease relevance of SDC2

• Glioma cell expression of the cell-surface HSPG glypican-1 closely mirrored the FGF-2 coactivator activity [1].
• FGFR1 and anosmin-1 may interact via a HSPG dependent mechanism raising the possibility of interaction between two single gene defects cause similar phenotypic abnormalities [2].
• Considering the important role of HSPG in maintaining the glomerular charge barrier, cell proliferation, and matrix interaction, downregulation of the production of this molecule by increased local AngII concentrations could have important consequences, such as albuminuria and matrix expansion [3].
• One step by which HSV-1 enters the cell is through binding to surface heparan sulfate proteoglycans (HSPG), a process that can be inhibited by fibroblast growth factor 2 (FGF-2) [4].
• Through the generation of AAV2-AAV8 hybrids and the creation of site-directed mutations, we mapped the domain that directs the activation of T cells to the RXXR motif on VP3, which was previously shown to confer binding of the virion to heparan sulfate proteoglycan (HSPG) [5].

High impact information on SDC2

• Of the various affinity-purified HSPGs tested, perlecan, the large basement membrane HSPG, is found to induce high affinity binding of bFGF both to cells deficient in HS and to soluble FGF receptors [6].
• This conclusion is based on the findings that IP-10 binding to cells is: (a) inhibited by heparin and heparan sulfate; (b) sensitive to a 1 M NaCl wash; (c) eliminated by treatment with heparinase and trypsin; and (d) absent on mutant CHO cells that do not express cell surface HSPG [7].
• This binding site has a Kd of 25 nM, is inhibited by recombinant murine or human IP-10, and is dependent on the presence of cell surface heparan sulfate proteoglycans (HSPG) [7].
• The transmembrane and cytoplasmic domains, in contrast, are highly similar to the corresponding domains of fibroglycan and syndecan, the two cell surface proteoglycans that figured as models for the design of the antisense primer [8].
• We conclude that the structural specificity of stromal HSPG that determines the selective colocalization of cytokines and ECM components leads to the formation of discrete niches, thereby orchestrating the controlled growth and differentiation of stem cells [9].

Chemical compound and disease context of SDC2

• We generated a novel p16/retinoblastoma pathway-dependent CRAd, Ad5.pK7-Delta24, with a polylysine motif in the fiber C-terminus, enabling CAR-independent binding to heparan sulfate proteoglycans (HSPG) [10].
• Detection in purified virus preparations of a neo-epitope generated by heparinase III confirmed the presence of virus-associated HSPG [HS (heparan sulfate) proteoglycan], acquired from the producer cell [11].

Biological context of SDC2

• A dosage effect of the GRPR and a position effect of the SDC2 gene may, however, contribute the phenotype observed in this patient since the orientation of these genes with respect to the translocation was incompatible with the formation of a fusion gene [12].
• Our recent observation that long-term in vitro human hematopoiesis requires a stromal heparan sulfate proteoglycan (HSPG) led us to hypothesize that such HSPG may orchestrate the formation of the stem cell niche [9].
• The expression of fibroglycan was weak in the early embryo, culminated during the morphogenetic phase and at the moment of cell lineage differentiation, and persisted in the perichondrium, periosteum and connective tissue cells [13].
• Spatial and temporal changes in the expression of fibroglycan (syndecan-2) during mouse embryonic development [13].
• In addition, rescue of kinase activity with a construct coding, the PKCdelta catalytic domain (CAT) reduced SYND2-induced apoptosis [14].

Anatomical context of SDC2

• Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblast growth factor action [15].
• We reveal that activated human macrophages express only a single major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan) as the result of de novo RNA and protein synthesis [15].
• The mammary epithelial cells, in contrast, expressed large amounts of a hybrid proteoglycan and heparan sulfate proteoglycans with core proteins of approximately 35 and 64 kDa, but the fibroglycan and 125-kDa cores were not detectable in these cells [16].
• Further characterization by affinity chromatography on immobilized monoclonal antibodies and by Northern blot analysis provided evidence for the expression of syndecan, glypican, and fibroglycan in human endothelial cells [17].
• Specific mRNA for the large basement membrane HSPG (perlecan) decreased, whereas mRNA for TGF-beta increased after incubation with AngII [3].

Associations of SDC2 with chemical compounds

• Lung fibroblasts expressed heparan sulfate proteoglycans with core proteins of approximately 35, 48/90 (fibroglycan), 64 (glypican), and 125 kDa and traces of a hybrid proteoglycan which carried both heparan sulfate and chondroitin sulfate chains [16].
• This study approaches the question of whether angiotensin II (AngII) and transforming growth factor beta (TGF-beta) are important mediators for mesangial heparan sulfate proteoglycan (HSPG) production [3].
• Blockade of the Subtype 1 Ang-II receptor (ATR1) reversed both the effects of AngII on HSPG and TGF-beta production [3].
• Other membrane-bound proteoglycans, like fibroglycan (45 kDa core) and the HS-proteoglycans with 90 and 130 kDa cores, as well as the CS/DS-proteoglycan with a 90 kDa core, were all of high hydrophobicity [18].
• In SYND2-transfected cells, the increase in PKCdelta was restricted to the cytosolic compartment, threonine 505-PKCdelta was underphosphorylated and immunoprecipitated PKCdelta showed decreased capacity to phosphorylate histone, indicating that SYND2 decreased PKCdelta activity [14].

Physical interactions of SDC2

• We conclude that the C-terminal folding domain of human LpL has a site for binding to heparin and to HSPG, presumably involving amino acids within residues 404-430 [19].
• The second pathway is composed of antithrombin III (ATIII) bound to heparan sulfate proteoglycan (HSPG) molecules on endothelial cells [20].

Other interactions of SDC2

• Moreover, affinity-purified glypican, but not syndecan or fibroglycan, elicited efficient conversion of plasmin-treated thrombin into an adhesive molecule [21].
• Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3' to the SDC2 gene [12].
• Anosmin-1 has an obligate functional interaction with membrane associated heparan sulphate proteoglycans (HSPG) and FGFR-1 (KAL-2) whose mutations lead to the autosomal dominant form of KS (AKS) [2].
• Whereas it is established that the C-terminal folding domain binds to alpha2MR/LRP, it remains uncertain whether it binds to heparin and to HSPG [19].
• Four different vertebrate syndecans, designated as syndecans 1-4 (or syndecan, fibroglycan, N-syndecan and amphiglycan, respectively), are known [22].

Analytical, diagnostic and therapeutic context of SDC2

• Moreover, heparitinase digestion of 125I-HSPG purified by affinity chromatography on an immobilized monoclonal antibody yielded only the Mr 64,000 protein [23].
• Northern blots failed to detect a message for fibroglycan in the mammary epithelial cells and in several other epithelial cell lines tested, while confirming the expression of both glypican and syndecan in these cells [16].
• These antibodies specifically recognize the 90- and 48-kDa core proteins on Western blots of total cellular extracts of human lung fibroblast HSPG [24].
• In situ hybridization analyses confirmed these expression patterns at the transcriptional level, identifying mesenchymal cells as the major source of fibroglycan production [13].
• Expression of heparan sulfate proteoglycan core protein was studied by RT-PCR and flow cytometry [25].

References