Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoiesis is regulated by two sets of signals, those generated by cytokines and those generated when precursor cells interact with bone marrow (BM) stroma. The intimate contact between precursors and stroma appears to be mediated by multiple, different receptor-ligand binding events. To identify receptor-ligand pairs mediating the adhesion of hematopoietic precursor cells to stroma, an in vitro model of hematopoiesis was used. This involved coculturing the BM-derived, interleukin-3 (IL-3)-dependent, multipotential cells, FCDP-mix A4 (A4) with a stromal equivalent embryonic mesenchymal cell line, Swiss 3T3 (3T3). In coculture, A4 cells survive, proliferate, and differentiate in the absence of exogenous IL-3, providing they are attached to the 3T3 cell surface. By using detergent lysates of surface-biotinylated A4 cells, A4 cell molecules that bind to the stroma could be detected by either fluorescein isothiocyanate (FITC)-streptavidin or FITC-antibody staining and flow cytometry. Using this approach the beta 2 integrin, Mac-1, and CD45, a receptor-type tyrosine phosphatase, were identified as molecules on the A4 cell surface that bind 3T3 cells. Various glycosaminoglycans (GAGs), particularly heparin and heparan sulfate, blocked binding of A4 cell surface molecules to the 3T3 cells. The binding of CD45 and Mac-1 to the 3T3 cells was similarly blocked by these GAGs. Removal of heparin-binding molecules from A4 cell lysates diminished binding to the 3T3 cells and digestion of the 3T3 cell surface with heparinase abolished the binding of CD45 and Mac-1. The data suggest that heparan sulfate on the 3T3 cell surface is a ligand for both CD45 and Mac-1, but the two molecules recognize different heparan sulfate structural motifs.
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PMID:Mac-1 (CD11b/CD18) and CD45 mediate the adhesion of hematopoietic progenitor cells to stromal cell elements via recognition of stromal heparan sulfate. 804 62

Midkine (MK), a retinoic acid-inducible heparin-binding protein, is a mitogen which initiates a cascade of intracellular protein tyrosine phosphorylation mediated by the JAK/STAT pathway after binding to its high affinity p200(+)/MKR cell surface receptor in the G401 cell line [Ratovitski, E. A. (1998) J. Biol. Chem. 273, 3654-3660]. In this study, we determined the biophysical characteristics of purified recombinant murine MK and analyzed the requirements for ligand multimerization and cell surface proteoglycan binding for the G401 cell mitogenic activity of MK. Our studies indicate that the secreted form of MK (M = 13 kDa) exists in solution as an asymmetric monomer with a frictional coefficient of 1. 48 and a Stokes radius of 23.7 A. By constructing bead models of MK using the program AtoB and the program HYDRO to predict the hydrodynamic properties of each model, our data suggest that MK has a dumb-bell shape in solution composed of independent N- and C-terminal domains separated by an extended linker. This asymmetric MK monomer is a biologically active ligand with mitogenic activity on G401 cells in vitro. Neither heparin-induced formation of noncovalent MK multimers nor tissue transglutaminase II covalent multimerization of MK enhanced MK mitogenic activity in this system. Since neither heparin competition nor cell treatment with chondroitinase ABC or heparinase III abolished the mitogenic effects of MK on G401 cells, cell-surface proteoglycan binding by MK does not appear to be a requirement for its observed mitogenic effects. These results provide strong evidence that the MK-specific p200(+)/MKR has distinctive biochemical properties which distinguish it from the receptor tyrosine phosphatase cell-surface proteoglycan PTPzeta/RPTPbeta and support the hypothesis that the diverse biological effects of MK are mediated by multiple cell-specific signal transduction receptors.
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PMID:Monomeric midkine induces tumor cell proliferation in the absence of cell-surface proteoglycan binding. 1082 69

PTPsigma is a receptor tyrosine phosphatase that is expressed widely in the developing nervous system and that controls the growth and retinotopic mapping of retinal axons. PTPsigma is also expressed in motor neurons where its function is unclear. Given that invertebrate relatives of PTPsigma can control motor axon guidance, target contact, and synaptogenesis, we have asked if extracellular ligands exist for cPTPsigma, the avian PTPsigma orthologue, in the neuromuscular system. Of the two major isoforms cPTPsigma1 and cPTPsigma2, only the shorter cPTPsigma1 isoform is expressed in developing spinal motor neurons and their axons. We show that ectodomains of cPTPsigma1, but not of cPTPsigma2, bind specifically to developing skeletal myotubes. The putative myotube ligand is not related to the previously described binding of cPTPsigma to heparan sulfates within the proteoglycans agrin and collagen XVIII, since heparinase treatment of myotubes does not alter cPTPsigma1 binding and since most mutations that abolish binding of cPTPsigma1 to heparin do not affect myotube binding. The expression of cPTPsigma1 in motor axons and its direct binding to target myotubes suggest an isoform-specific role for axonally expressed cPTPsigma1 during establishment or maintenance of neuromuscular contacts.
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PMID:Isoform-specific binding of the tyrosine phosphatase PTPsigma to a ligand in developing muscle. 1259 37