title: Pentosan polysulfate, a potent anti HIV and anti tumor agent, inhibits protein serine/threonine and tyrosine kinases.
abstract: Pentosan polysulfate, a polyanionic mucopolysaccharide, which has been shown to exert inhibitory effects on human immunodeficiency virus (HIV-I) replication, inhibited the activities of protein tyrosine kinases from lymphocytes (Jurkat cells) and rat lung in a concentration dependent manner. In addition, the autophosphorylation of p56lck, a lymphocyte associated protein tyrosine kinase from Jurkat cells was also inhibited by pentosan polysulfate (100 micrograms/ml). Furthermore, the activities of protein serine/threonine kinases such as Ca2+, phospholipid-dependent protein kinase (protein kinase C) from human platelets and the catalytic subunit of cAMP-dependent protein kinase from skeletal muscle were also inhibited by this mucopolysaccharide. However, the activity of phosphorylase kinase was not altered. The inhibition of rat lung protein tyrosine kinase was rapid and competitive with respect to ATP with an apparent Ki value of 5-20 micrograms/ml. These results suggest that the ability of pentosan polysulfate to inhibit various protein serine/threonine and tyrosine kinases may be one of the mechanisms by which this compound exerts its inhibitory effect of HIV-I replication.
authors.affiliation: Department of Medicine, University of Montreal, Québec, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: R P
authors.initials: RP
authors.lastname: Sékaly
authors.forename: J L
authors.initials: JL
authors.lastname: Chiasson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000201:enzymology; D009124:Muscle Proteins / Q000037:antagonists & inhibitors; D009132:Muscles / Q000201:enzymology; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D010764:Phosphorylase Kinase / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; D010426:Pentosan Sulfuric Polyester; D010764:Phosphorylase Kinase; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C