Christopher Pinko

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BACKGROUND Angiogenesis is involved in tumor growth, macular degeneration, retinopathy and other diseases. Vascular endothelial growth factor (VEGF) stimulates angiogenesis by binding to specific receptors (VEGFRs) on the surface of vascular endothelial cells. VEGFRs are receptor tyrosine kinases that, like the platelet-derived growth factor receptors(More)
Proteolytic processing of capsid assembly protein precursors by herpesvirus proteases is essential for virion maturation. A 2.5 A crystal structure of the human cytomegalovirus protease catalytic domain has been determined by X-ray diffraction. The structure defines a new class of serine protease with respect to global-fold topology and has a catalytic(More)
We have examined the expression of a cAMP pulse-repressed and two cAMP pulse-induced genes in response to cAMP and caffeine under a number of different physiological conditions, and in several classes of development mutants altered in cAMP-mediated signal transduction pathways. The data presented help characterize the mutants with regard to early gene(More)
Vascular endothelial growth factor (VEGF) is a dimeric protein which induces formation of new blood vessels (angiogenesis) through binding to VEGF-receptor-2 tyrosine kinase (VEGFR2 TK) or KDR (kinase insert domain-containing receptor) on the surface of endothelial cells. Angiogenesis has been shown to be essential for malignancy of tumors; therefore,(More)
The single-chain 28 kDa human cytomegalovirus (HCMV) protease catalytic domain containing the A143Q mutation has been kinetically and conformationally characterized. The specific activity of the HCMV A143Q protease (HCMVp) increases as the protease concentration increases, suggesting that this protease oligomerizes at high protein concentration to form a(More)
We report here the production of active recombinant single-chain human cytomegalovirus protease in Escherichia coli and development of a continuous assay for this protease. In order to produce the human cytomegalovirus (HCMV) protease for structural studies and accurate kinetic analysis, mutation of alanine 143 at an internal cleavage site was introduced to(More)
DNA ligase is an enzyme important for DNA repair and replication. Eukaryotic genomes encode ligases requiring ATP as the cofactor; bacterial genomes encode NAD(+)-dependent ligase. This difference in substrate specificities and the essentiality of NAD(+)-dependent ligase for bacterial survival make NAD(+)-dependent ligase a good target for designing highly(More)
We have previously shown that the developmentally regulated gene D2 is induced during aggregation by pulses of cAMP, which act via the cell surface receptor and consequent signal transduction pathways (W. Rowekamp and R.A. Firtel, 1980, Dev. Biol. 79, 409-418; S.K.O. Mann and R.A. Firtel, 1987, Mol. Cell. Biol. 7, 458-469; S.K.O. Mann, C. Pinko, and R.A.(More)
Activation of receptor tyrosine kinases by autophosphorylation is one of the most common and critical transformations in signal transduction, yet its role in catalysis remains controversial. Autophosphorylation of the angiogenic receptor tyrosine kinase Tie2 was studied in terms of the autophosphorylation sites, sequence of phosphorylation at these sites,(More)
The nucleotide sequence of the human cytomegalovirus (HCMV) protease gene from two laboratory strains and seven clinical isolates, both ganciclovir-sensitive and -resistant, was examined to determine the genetic variability of the HCMV protease catalytic domain and to identify changes that may alter the efficacy of designed protease inhibitors. The Towne(More)