Current Cancer Research For other titles published in this series, go to www. I am heartily thankful to Dr. Oncogene advance online publication, 9 November 2015; doi:10. In summary, bioinformatics analysis has provided hypotheses for new modes of potential therapy based on morphometric subtyping. Conformationally constrained analogues of diacylglycerol. The Journal Biological Chemistry, 275 14 , 10697—10701. The Journal of Biological Chemistry, 280, 24363—24370.
Note that the affinity of each membrane-targeting module of conventional protein kinase C isozymes, the C1 and C2 domains, is too low to allow pseudosubstrate release in response to physiological levels of diacylglycerol or Ca2+ alone. Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester. Increased membrane affinity of the C1 domain of protein kinase C delta compensates for the lack of involvement of its C2 domain in membrane recruitment. We conclude that the capillary isoelectric focusing immunoassay system may provide a window into the integrated consequences of ligand binding and thus afford a powerful platform for compound development. Zinc Finger Domains and Phorbol Ester Pharmacophore: Analysis of binding to mutated form of protein kinase C z and the vav and c-raf proto-oncogene products.
Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1, 4, 5-trisphosphate. The mechanism s of chemoresistance is are often multifactorial. It should now be possible to identify the specific groups responsible for this activity and potentially to open the way to the design of much simplified molecules incorporating these structural features. This multiplicity of contributing elements discussed above provides great opportunities for diversity. The Journal of Cell Biology, 161 5 , 899—909. Protein Kinase C in Cancer Signaling and Therapy is composed of twenty-three chapters written by leading experts in the field. The Journal of Cell Biology, 139, 351—363.
A limitation in the analysis of selectivity for isolated C1 domains, as distinct from selectivity for the intact receptors, is that this selectivity may not carry over to the intact proteins. The nucleotide-binding site of human sphingosine kinase 1. Antiangiogenic effects of a protein kinase Cbeta-selective small molecule. Aplysiatoxin is a polyacetate Fujiki and Sugimura 1987. Phosphorylation on this Thr correctly aligns residues for catalysis.
Lipid structure and not membrane structure is the major determinant in the regulation of protein kinase C by phosphatidylserine. The function of dynamin in endocytosis. Journal of Biological Chemistry, 272, 7390—7397. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The Journal of Biological Chemistry, 269, 11590—11594. Proceedings of the National Academy of Sciences of the United States of America, 83, 8535—8539.
Biochemical Society Transactions, 23 1 , 153—155. . Proc Natl Acad Sci U S A. Their high octanol—water partition coefficient log P dictates that they will not be free in aqueous solution at an appreciable concentration. Biochimica et Biophysica Acta, 1761, 827—837. Identification and characterization of zinc binding sites in protein kinase C.
DgkA is an integral membrane protein, with three membrane-spanning domains Loomis et al. Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase C delta. Investigational New Drugs, 20, 241—251. The third and last phosphorylation on the hydrophobic motif occurs by intramolecular autophosphorylation. Protein kinase Cepsilon interacts with signal transducers and activators of transcription 3 Stat3 , phosphorylates Stat3Ser727, and regulates its constitutive activation in prostate cancer.
Critical Reviews in Toxicology, 8, 199—234. The concept of the hydrophobic switch makes the strong prediction that ligand binding and receptor activation are coupled to the energy constraints of the overall conformational change induced by the switching mechanism. Cloning of an intracellular receptor for protein kinase C: A homology of the b subunit of G proteins. Signaling roles of diacylglycerol kinases. Molecular and Cellular Biology, 22, 5897—5911.