C1 Domain (c1 + domain)

Distribution by Scientific Domains
Chemistry50%
Life Sciences33%

Selected Abstracts

Importance of Interaction between C1 Domain and Lipids in Protein Kinase C, Activation: Hydrophobic Side Chain Direction in Isobenzofuranone Ligands Controls Enzyme Activation Level

CHEMMEDCHEM, Issue 7 2007
Go Hirai Dr.
Substituent direction is important: Type A,D isobenzofuranone derivatives were synthesized with differently directed hydrophobic alkyl side chains. These ligands bind in a similar conformation to protein kinase C, but have contrasting activation abilities, possibly owing to different interaction of the side chain with the membrane lipid. [source]

Tyr2105Cys mutation in exon 22 of FVIII gene is a risk factor for the development of inhibitors in patients with mild/moderate haemophilia A

HAEMOPHILIA, Issue 4 2006
M. FRANCHINI
Summary., We report the case of a patient with mild haemophilia A, due to a Tyr2105Cys mutation in exon 22 of the C1 domain, who developed a high-titre factor VIII inhibitor (maximum titre 1600 BU) with recurrent severe haemorrhages and fatal intracranial bleeding. Based on published data, it appears that although this mutation occurs rarely in patients with mild or moderate haemophilia A, it is frequently associated with the development of high-titre inhibitors. [source]

Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic , cells

THE JOURNAL OF PHYSIOLOGY, Issue 1 2004
Hui Zhang
The present study was conducted to evaluate the role of conventional protein kinase C (PKC) in calcium-evoked insulin secretion. In rat , cells transfected with green fluorescent protein-tagged PKC-, (PKC-,,EGFP), a depolarizing concentration of potassium induced transient elevation of cytoplasmic free calcium ([Ca2+]c), which was accompanied by transient translocation of PKC-,,EGFP from the cytosol to the plasma membrane. Potassium also induced transient translocation of PKC-,,EGFP, the C1 domain of PKC-, and PKC-,,GFP. A high concentration of glucose induced repetitive elevation of [Ca2+]c and repetitive translocation of PKC-,,EGFP. Diazoxide completely blocked both elevation of [Ca2+]c and translocation of PKC-,,EGFP. We then studied the role of conventional PKC in calcium-evoked insulin secretion using rat islets. When islets were incubated for 10 min with high potassium, Gö-6976, an inhibitor of conventional PKC, and PKC-, pseudosubstrate fused to antennapedia peptide (Antp-PKC19,31) increased potassium induced secretion. Similarly, insulin release induced by high glucose for 10 min was enhanced by Gö-6976 and Antp-PKC19,31. However, when islets were stimulated for 60 min with high glucose, both Gö-6976 and Antp-PKC19,31 reduced glucose-induced insulin secretion. Similar results were obtained by transfection of dominant-negative PKC-, using adenovirus vector. Taken together, PKC-, is activated when cells are depolarized by a high concentration of potassium or glucose. Conventional PKC is inhibitory on depolarization-induced insulin secretion per se, but it also augments glucose-induced secretion. [source]

A missense mutation (p.Leu2153His) of the factor VIII gene causes cattle haemophilia A

ANIMAL GENETICS, Issue 5 2009
M. Khalaj
Summary Two cases of hereditary bleeding disorder diagnosed as haemophilia A were recently observed in Japanese Brown cattle. We sequenced the entire coding region of the factor VIII gene of the affected animals to find a causative mutation. A nucleotide substitution of T to A resulting in an amino acid substitution of leucine to histidine (p.Leu2153His) was identified in a highly conserved residue in the C1 domain of factor VIII. Genotyping of 254 normal animals including the pedigree of the affected animals and randomly sampled animals of different breeds confirmed that the substitution is the causative mutation of cattle haemophilia A. [source]

Toward the development of new medicinal leads with selectivity for protein kinase C isozymes

THE CHEMICAL RECORD, Issue 4 2005
Kazuhiro Irie
Abstract Tumor promoters such as phorbol esters bind strongly to protein kinase C (PKC) isozymes to induce their activation. Since each PKC isozyme is involved in diverse biological events in addition to tumor promotion, the isozymes serve as promising therapeutic targets. Tumor promoters bind to the C1A and/or C1B domain of conventional (,, ,I, ,II, and ,) and novel PKC isozymes (,, ,, ,, and ,). As these C1 domains play differential roles in PKC activation and their translocation in cells, the development of agents with binding selectivity for individual C1 domains is a pressing need. For this purpose, we established a synthetic C1 peptide library of all PKC isozymes. The library enabled us to identify indolactam-V (1) as a promising lead compound. Our diverse structure,activity studies on 1 indicated that the position of the hydrophobic substituent on the indole ring dominates the PKC isozyme- and C1 domain-selective binding rather than conformation of the nine-membered lactam. Moreover, we suggested that the indole ring of 1 could be involved in the CH/, interaction with Pro-11 of the C1B domain of PKC,. This invaluable information will lead to the structural optimization of the PKC, ligand as exemplified by the design and synthesis of naphtholactam-V8 (21). © 2005 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 5: 185,195; 2005: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20044 [source]