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)

Close interaction of human hematopoietic progenitors with the bone marrow microenvironment is important for the ordered progression of human hematopoiesis. Progenitor cell adhesion to stroma has a complex molecular basis, involving various cell-extracellular matrix and cell-cell interactions. We have previously shown that adhesion of colony-forming cells (CFC) to fibronectin, present in stromal extracellular matrix, involves multiple sites, including two heparin-binding synthetic peptides (FN-C/H I and FN-C/H II) and the alpha 4 beta 1 integrin-binding peptide CS1. These synthetic peptides are located in close proximity in the type III repeat 14 and the immediately adjacent type IIIcs region of fibronectin. In the current study, we evaluate receptors expressed by CFC responsible for their adhesion to fibronectin. We show that the alpha 4 beta 1 integrin mediates adhesion to CFC to the peptides FN-C/H I and CS1. Adhesion of CFC to fibronectin is also mediated by proteoglycans, because removal of cell surface chondroitin-sulfate proteoglycans resulted in decreased adhesion of CFC to FN-C/ I and FN-C/H II. The core protein of this proteoglycan was identified by immunoprecipitation as a 90-kD member of the CD44 group of adhesion molecules. Interestingly, although the proteoglycan core protein failed to adhere to FN-C/H II affinity columns, anti-CD44 monoclonal antibodies blocked CFC adhesion to FN-C/H II, indicating that these monoclonal antibodies may interfere with core protein-mediated intracellular signalling. Finally, we show that CD44 and alpha 4 beta 1 may cooperate in establishing progenitor adhesion, because anti-CD44 antibodies potentiated the adhesion-inhibitory effects of suboptimal concentrations of anti-alpha 4 or anti-beta 1 monoclonal antibodies. These results provide a working model for progenitor cell recognition of fibronectin (and possibly the marrow micro-environment) in which the coordinated action of integrins and cell surface proteoglycans is necessary for cell adhesion. This model can now be used to study the complex relationship between progenitor cell adhesion and the regulation of their proliferation and differentiation.
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PMID:Adhesion of committed human hematopoietic progenitors to synthetic peptides from the C-terminal heparin-binding domain of fibronectin: cooperation between the integrin alpha 4 beta 1 and the CD44 adhesion receptor. 752 91

Sponges [phylum Porifera] form the basis of the metazoan kingdom and represent the evolutionary earliest phylum still extant. Hence, as living fossils, they are the taxon closest related to the hypothetical ancestor of all Metazoa, the Urmetazoa. Until recently, it was still unclear whether sponges are provided with a defined body plan. Only after the cloning, expression and functional studies of characteristic metazoan genes, could it be demonstrated that these animals comprise the structural elements which allow the sponge cells to organize themselves according to a body plan. Adhesion molecules involved in cell-cell and cell-matrix interactions have been identified. Among the cell-cell adhesion molecules the aggregation factor (AF) is the prominent particle. It is composed of a core protein that is associated with the adhesion molecules, a 36 kDa as well as a 86 kDa polypeptide. A galectin functions as a linker of the AF to the cell-membrane-associated receptor, the aggregation receptor (AR). The most important extracellular matrix molecules are collagen- and fibronectin-like molecules. These proteins interact with the cell-membrane receptors, the integrins. In addition, a neuronal receptor has been identified, which--together with the identified neuroactive molecules--indicate the existence of a primordial neuronal network already in Porifera. The primmorph system, aggregated cells that retain the capacity to proliferate and differentiate, has been used to demonstrate that a homeobox-containing gene, Iroquois, is expressed during canal formation in primmorphs. The formation of a body plan in sponges is supported by skeletal elements, the spicules, which are composed in Demospongiae as well as in Hexactinellida of amorphous, noncrystalline silica. In Demospongiae the spicule formation is under enzymic control of silicatein. Already at least one morphogen has been identified in sponges, myotrophin, which is likely to be involved in the axis formation. Taken together, these elements support the recent conclusions that sponges are not merely nonorganized cell aggregates, but already complex animals provided with a defined body plan.
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PMID:Analysis of the sponge [Porifera] gene repertoire: implications for the evolution of the metazoan body plan. 1582 38

Perlecan/HSPG2 is a large, multi-domain, multifunctional heparan sulfate proteoglycan with a wide tissue distribution. With the exception of its unique domain I, each of perlecan's other four domains shares sequence similarity to other protein families including low density lipoprotein (LDL) receptor, laminin alpha chain, neural cell adhesion molecule (NCAM), immunoglobulin (Ig) superfamily members, and epidermal growth factor (EGF). Previous studies demonstrated that glycosaminoglycan-bearing perlecan domain I supports early chondrogenesis and growth factor delivery. Other sites in the core protein interact with other matrix molecules and support cell adhesion, although the peptide sequences involved remain unidentified. To identify novel functional motifs within perlecan, we used a bioinformatics approach to predict regions likely to be on the exterior of the folded protein. Unique hydrophilic sequences of about 18 amino acids were selected for testing in cell adhesion assays. A novel peptide sequence (TWSKVGGHLRPGIVQSG) from an immunoglobulin (Ig) repeat in domain IV supported rapid cell adhesion, spreading and focal adhesion kinase (FAK) activation when compared to other peptides, a randomly scrambled sequence of the domain IV peptide or a negative control protein. MG-63 human osteosarcoma cells, epithelial cells and multipotent C(3)H10T1/2 cells, but not bone marrow cells, rapidly, i.e., within 30 min, formed focal adhesions and assembled an actin cytoskeleton on domain IV peptide. Cell lines differentially adhered to the domain IV peptide, suggesting adhesion is receptor specific. Adhesion was divalent cation independent and heparin sensitive, a finding that may explain some previously poorly understood observations obtained with intact perlecan. Collectively, these studies demonstrate the feasibility of using bioinformatics-based strategies to identify novel functional motifs in matrix proteins such as perlecan.
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PMID:A novel peptide sequence in perlecan domain IV supports cell adhesion, spreading and FAK activation. 1799 86