Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin affin regulatory peptide (HARP), also called Pleiotrophin (PTN), is a polypeptide that displays a high affinity for heparin and that shares approximately 50% sequence homology with Midkine (MK). According to this structural homology, these two molecules constitute a new family of heparin-binding proteins. The biological properties of HARP and MK remain largely a subject of debate. Both proteins have been described as neurite outgrowth promoting agents whereas until recently the mitogenic activity has been controversial. The aim of this review is to summarize the information on HARP with special focus on the recent data relating to its mitogenic properties.
 ...
PMID:Biochemical and mitogenic properties of the heparin-binding growth factor HARP. 871 67

A new endogenous proteinase inhibitor from the cell-free hemolymph of a solitary ascidian, Halocynthia roretzi, was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography on Ether-Toyopearl and affinity chromatography on Heparin-Sepharose. The purity of the inhibitor was examined by SDS-PAGE, gel-permeation chromatography, reversed-phase chromatography, isoelectric focusing, immunological analysis and amino-terminal amino acid sequence analysis. The inhibitor is a single polypeptide chain whose molecular weight, isoelectric point and the first 10 amino-terminal amino acid sequences are 58 kDa, pI 9.2 and NH2-Thr-Lys-Lys-Asp-Gly-Glu-Glu-Lys-Val-Ala, respectively. The purified protein inhibits plasma enzyme(s) of H. roretzi, and the rate of inhibition to the plasma enzyme(s) activity was accelerated by incubation with dextran sulfate, but the effect was neutralized by further incubation with polycation, such as polybrene or protamine sulfate. The inhibitory activity was not affected appreciably by pH 7-10 but ceased completely below pH 5 or by heating at 50 degrees C for 30 min.
 ...
PMID:Purification and characterization of a 58,000-Da proteinase inhibitor from the hemolymph of a solitary ascidian, Halocynthia roretzi. 875 95

Five major polypeptides of 70, 50, 47, 19 and 17 kDa and four minor polypeptides (100, 65, 45 and 39 kDa) become phosphorylated when clathrin-coated vesicles (CCV) from zucchini hypocotyls are incubated in [gamma 32P]Mg-ATP. After dissociation with 0.5 M Tris/HCl the CCV coat polypeptides were subjected to gel filtration in order to separate clathrin triskelions from beta-adaptin-containing fractions. Only the latter bore kinase activities, with phosphorylated polypeptides of 39 kDa in addition to the 50, 19-kDa and 17-kDa polypeptides just mentioned. Heparin, an inhibitor of casein kinase II, permitted the phosphorylation of only the 19-kDa and 17-kDa polypeptides. Staurosporine, an inhibitor of protein kinase c-like activities, prevented the phosporylation of the 70-kDa polypeptide. When recombined with the triskelions the beta-adaptin fractions achieved the phosphorylation of the 45-kDa and 70-kDa polypeptides. Because of its heat stability and calcium-binding properties we interpret the 45-kDa polypeptide as being a clathrin light chain. Antibodies raised against the 70-kDa group of heat-shock proteins (Hsp70) recognize a 70-kDa polypeptide in the beta-adaptin-containing fractions. Because this polypeptide only phosphorylates in the presence of triskelions we consider it to be the uncoating ATPase, which is known to aggregate upon dissociation of the CCV coat. Our results therefore indicate that zucchini CCV contain a number of phosphorylable polypeptides equivalent to the beta, mu and sigma adaptins of bovine brain. Just as in bovine brain CCV a casein-kinase-II-like activity is associated with the zucchini CCV 50/47-kDa polypeptides, further pointing to their identity as plant mu2/mu1 adaptin equivalents.
 ...
PMID:Localization and properties of kinases in clathrin-coated vesicles from zucchini hypocotyls. 885 56

The sulfated polysaccharide heparin interacts with both poly-L- and poly-D-lysine, promoting the alpha-helix conformation in the polypeptide. Chemically modified heparins in which one of the three sulfate groups per disaccharide has been removed form the same type of complex with poly-L-lysine; when two of the three sulfate groups are removed this property is lost. Heparin oligosaccharides as small as the octasaccharide can still promote alpha-helix in poly-L-lysine; the hexa- and tetrasaccharides do not, but they do disturb to a lesser extent the dynamic conformation equilibrium associated with poly-L-lysine at pH7 (22 degrees C). A three-dimensional structure for the heparin/polylysine complex is proposed in which the helical heparin molecule and the alpha-helical polypeptide are side-by-side, not intertwining. The regular periodicity of sulfate group clusters along one side of the polysaccharide chain matches the periodicity of the polypeptide alpha-helix, allowing electrostatic interactions every three peptide turns between a heparin sulfate cluster and a zeta-amino group of the polylysine. The heparin octasaccharide is the smallest even-numbered oligosaccharide long enough for two such interactions to take place.
 ...
PMID:The interaction between heparin and polylysine: a circular dichroism and molecular modelling study. 907 Mar 84

Heparan sulphate binding to cells of the gastric pathogen Helicobacter pylori at pH 4-6 is common. Binding was inhibited by various unlabelled sulphated polysaccharides and at high ionic strength and pH, but not by carboxylated or non-sulphated compounds. The inhibition by various sulphated compounds such as dextran sulphate and carrageenans was related to the sulphate content and not to the carbohydrate polymer backbone. The IC50 values for heparin and dextran sulphate for H. pylori strain 25 were calculated as 3.55 x 10(-7) M and 5.01 x 10(-6) M respectively. Heparin-binding proteins of H. pylori are exposed on the cell surface, as shown by biotinylation of cell-surface proteins before separation of outer membranes and by an indirect immunofluorescence assay. The strongest biotin-heparin binding by H. pylori was observed with a polypeptide in the 55-60 kDa region.
 ...
PMID:Identification of heparan sulphate binding surface proteins of Helicobacter pylori: inhibition of heparan sulphate binding with sulphated carbohydrate polymers. 923 37

A soluble, cytoplasmic protein kinase was purified from the developing seeds of winged bean (Psophocarpus tetragonolobus) following conventional methods of protein purification including anion-exchange chromatography, gel-filtration and Blue Sepharose chromatography. The purified enzyme consists of a single polypeptide of M(r) 45,000 as determined by SDS-PAGE and gel-filtration chromatography on Sephacryl S-200. The pH optimum of the protein kinase activity was 7.0, while the optimum concentration of Mg2+ was 5 mM. The enzyme utilised casein as an exogenous phosphate acceptor. The conventional modulators of protein kinases, including the cyclic nucleotides, Ca2+ and calmodulin, did not stimulate the purified enzyme. Heparin and spermine, too, had no effect on its activity. Phosphoamino acid analysis revealed that the enzyme transferred the gamma-phosphate of ATP only to serine residues of casein. All these characteristics, taken together, classifies the purified protein kinase as a member of the casein kinase I group of enzymes.
 ...
PMID:Purification and characterisation of a protein kinase from winged bean. 933 24

Heparin is a highly sulfated polysaccharide consisting of a repeating disaccharide structure as found in other glycosaminoglycanes. The intravenous and subcutaneous formulation of the drug is routinely used for its well-known, time-honored antithrombotic effect. However, available evidences linking heparin to angiogenesis raise the possibility of a therapeutically relevant antiischemic effect of the drug. Molecular biology data show that in a hypoxic milieu heparin could facilitate angiogenesis through interactions with a family of polypeptide growth factor mitogens that stimulate endothelial cell proliferation. Experimental data suggest that heparin can augment collateral circulation when combined with other potentially angiogenetic factors, such as repeated ischemia, coronary occlusion, or physical exercise. Clinical data, although very initial, encompassing a total of only 41 heparin-treated patients with coronary artery disease, suggest that heparin facilitates collateral development stimulated by exercise-induced myocardial ischemia in humans. According to the heparin-collateral hypothesis, the mechanism of action of heparin as an antiischemic medication would be independent of its anticoagulant action. The molecular targets of heparin are Factor Xa and IIa for antithrombotic action, heparin-binding growth factors (including fibroblast growth factor and vascular endothelial growth factor) for angiogenesis. The antithrombotic effect is not linked to a cellular target, whereas the angiogenetic effect directly stimulates endothelial cells. The molecular cofactor required for effect is antithrombin III for antithrombosis, and possibly endogenous adenosine for angiogenesis. The therapeutic effect is achieved within minutes or hours for antithrombosis, and within weeks or months for angiogenesis.
 ...
PMID:The coronary angiogenetic effect of heparin: experimental basis and clinical evidence. 937 49

Heparin affin regulatory peptide (HARP), also named pleiotropin, is a secreted polypeptide that belongs to a new family of heparin-binding growth/differentiation factors. In this study, we investigated the expression and distribution of HARP mRNA and protein in rat uterus. Semi-quantitative reverse transcriptase PCR experiments showed variations in HARP mRNA levels throughout the estrous cycle, with a maximum during diestrus, pointing to hormonal regulation of HARP mRNA expression. Uterine expression of HARP mRNA was studied in ovariectomized animals treated with 17 beta-estradiol, progesterone alone or progesterone and RU486. In these experiments, progesterone upregulated HARP mRNA expression. Induction was observed 6 h after progesterone injection and was inhibited by RU486 treatment. In contrast, after 17 beta-estradiol injection, a slight decrease in HARP mRNA expression was observed. In situ hybridization studies with digoxigenin-labeled DNA probe revealed that HARP mRNA was present in smooth muscle cells of both myometrium and blood vessels and also in endothelial cells from endometrium. Immunohistochemical studies showed that HARP expression was not limited to cells that expressed HARP mRNA, but also occurred in both the luminal and glandular epithelium even though its transcript was never detected. We conclude that HARP may mediate the effects of progesterone on the homeostasis and vascularization of uterine tissue.
 ...
PMID:Upregulation of the angiogenic factor heparin affin regulatory peptide by progesterone in rat uterus. 984 68

Heparin affin regulatory peptide (HARP) is a polypeptide belonging to a family of heparin binding growth/differentiation factors. The high affinity of HARP for heparin suggests that this secreted polypeptide should also bind to heparan sulfate proteoglycans derived from cell surface and extracellular matrix defined as extracellular compartments. Using Western blot analysis, we detected HARP bound to heparan sulfate proteoglycans in the extracellular compartments of MDA-MB 231 and MC 3T3-E1 as well as NIH3T3 cells overexpressing HARP protein. Heparitinase treatment of BEL cells inhibited HARP-induced cell proliferation, and the biological activity of HARP in this system was restored by the addition of heparin. We report that heparan sulfate, dermatan sulfate, and to a lesser extent, chondroitin sulfate A, displaced HARP bound to the extracellular compartment. Binding analyses with a biosensor showed that HARP bound heparin with fast association and dissociation kinetics (kass = 1.6 x 10(6) M-1 s-1; kdiss = 0.02 s-1), yielding a Kd value of 13 nM; the interaction between HARP and dermatan sulfate was characterized by slower association kinetics (kass = 0.68 x 10(6) M-1 s-1) and a lower affinity (Kd = 51 nM). Exogenous heparin, heparan sulfate, and dermatan sulfate potentiated the growth-stimulatory activity of HARP, suggesting that corresponding proteoglycans could be involved in the regulation of the mitogenic activity of HARP.
 ...
PMID:Glycosaminoglycans differentially bind HARP and modulate its biological activity. 1007 64

Heparin affin regulatory peptide (HARP), also called pleiotrophin (PTN), is a secreted polypeptide which binds to heparin and plays a key role in cellular growth and differentiation. In order to assess the determinants potentially important to its biological activity, we tested the ability of HARP to oligomerize, a process involved in mitogenic activity of the heparin-binding fibroblast growth factor. Using dissuccinimidyl suberate cross-linking experiments and affinity chromatography, we report that human HARP forms noncovalent dimers. Dimerization is dependent on the presence of heparin or other sulfated glycosaminoglycans, as chlorate treatment of cells inhibits this process. In vitro, different glycosaminoglycans, such as dermatan sulfate and chondroitin sulfate-C, also induce a dimer assembly of HARP. The relevance of this process was supported by experiments demonstrating that HARP is secreted as a dimer in conditioned medium of NIH-3T3 cells that overexpressed this growth factor and is also associated to the cell surface or to the extracellular matrix.
 ...
PMID:Glycosaminoglycans promote HARP/PTN dimerization. 1060 May 21


<< Previous 1 2 3 4 5 6 7 Next >>