Linked Life Data

7533846

Source:http://linkedlifedata.com/resource/pubmed/id/7533846

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-4-10
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
457-73
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7533846-Amino Acid Sequence, pubmed-meshheading:7533846-Animals, pubmed-meshheading:7533846-Brain, pubmed-meshheading:7533846-Cell Adhesion, pubmed-meshheading:7533846-Cell Adhesion Molecules, pubmed-meshheading:7533846-Cell Adhesion Molecules, Neuronal, pubmed-meshheading:7533846-Cell Survival, pubmed-meshheading:7533846-Cells, Cultured, pubmed-meshheading:7533846-Chromatography, Affinity, pubmed-meshheading:7533846-Collagen, pubmed-meshheading:7533846-Fibronectins, pubmed-meshheading:7533846-Glycoproteins, pubmed-meshheading:7533846-Heparin, pubmed-meshheading:7533846-Horses, pubmed-meshheading:7533846-Humans, pubmed-meshheading:7533846-Laminin, pubmed-meshheading:7533846-Macromolecular Substances, pubmed-meshheading:7533846-Molecular Sequence Data, pubmed-meshheading:7533846-Oligodendroglia, pubmed-meshheading:7533846-Phosphorylation, pubmed-meshheading:7533846-Polylysine, pubmed-meshheading:7533846-Sequence Homology, Amino Acid, pubmed-meshheading:7533846-Sheep, pubmed-meshheading:7533846-Vitronectin
pubmed:year
1994
pubmed:articleTitle
GRASP: a novel heparin-binding serum glycoprotein that mediates oligodendrocyte-substratum adhesion.
pubmed:affiliation
Department of Neurology, University of Chicago, Illinois 60637.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't