Disease relevance of Dock3

• The relative effects of two beta-lactam antibiotics, penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime, upon in vitro induction of lipopolysaccharide (LPS) release were investigated against smooth- and rough-LPS mutant isolates of Pseudomonas aeruginosa [1].
• This study was undertaken to investigate if MOCA and substitutes, Polacure 740M, Ethacure 300, Cyanacure and Conacure have the potential to cause papillomas in a two stage initiation/promotion protocol in HRA/Skh hairless mice [2].
• MOCAP exposure showed symptoms of severe neurotoxicity coupled with serum chemistry changes in the absence of any significant genomic change or brain pathology [3].
• Recently, the bioavailability and mechanistic pathways of cytoprotection by GSPE were examined on acetaminophen-induced hepatotoxicity and nephrotoxicity, amiodarone-induced pulmonary toxicity, doxorubicin-induced cardiotoxicity, DMN-induced immunotoxicity and MOCAP-induced neurotoxicity in mice [4].

Psychiatry related information on Dock3

• PBP is localized to the particulate fraction of extracts of Alzheimer's disease brain but is found in the soluble fractions of brain from age matched normal controls [5].

High impact information on Dock3

• Adenoviral reconstitution of PBP in PBP(Liv-/-) mouse livers restored PB-mediated nuclear translocation of CAR as well as inducibility of CYP1A2, CYP2B10, CYP3A11, and CYP7A1 expression [6].
• PBP-deficient hepatocytes in liver failed to reveal PB-dependent translocation of CAR to the nucleus [6].
• CAR interacts with the two nuclear receptor-interacting LXXLL (L, leucine; X, any amino acid) motifs in PBP in a ligand-dependent manner [6].
• Here we demonstrate that MOCA binds to Rac1 and enhances its activity, which leads to the activation of c-Jun NH(2)-terminal kinase (JNK) and causes changes in cell morphology [7].
• MOCA is also concentrated with actin on the growth cone in primary cultures of cortical neurons [7].

Biological context of Dock3

• These observations suggest that MOCA may induce cytoskeletal reorganization and changes in cell adhesion by regulating the activity of Rac1 [7].
• In addition, the expression of PBP increases the phosphorylation of tau in cultured cells [5].
• The concentration of an epithelial androgen-dependent protein, the prostatic binding protein (PBP), expressed by the enlarged lobe of the rat VP was similar to that of the control lobe of rat VP [8].
• A three-dimensional Voronoi binding site model has been formulated from a series of competitors for the binding site on a recently isolated polycyclic aromatic hydrocarbon binding protein (PBP) from mouse liver [9].
• The kinetics and sequence of induction of PMP68 and PBP following a single dose of Wy-14,643 were compared and shown to be similar, and the effects were reversible [10].

Anatomical context of Dock3

• On poly-d-lysine-coated dishes, endogenous MOCA is concentrated on the leading edge of broad membrane protrusions (lamellipodia) where actin filaments are co-localized [7].
• It is shown here that PBP is associated with neurofibrillary tangles in Alzheimer's disease brain [5].
• The PBP was also present in liver cytosol from 7-week-old female and 42-week-old male C57Bl/6J mice [11].
• Thus peroxisome proliferators enhance the expression of the genes for both the membrane protein PMP68 and the matrix protein PBP, but the regulation of this expression appears to be mediated by different mechanisms [10].
• MOCA exposure caused a dose-dependent inhibition of natural immune activities (i.e. natural killer, NK and natural P815 killer, NPK) and mitogen-stimulated proliferation of T- and B-lymphocytes, with 50% inhibition (IC50) of splenic-cell activities occurring at 145, 85, 21 and 31 microM, respectively [12].

Associations of Dock3 with chemical compounds

• One approach has been to identify a beta-lactam with improved affinity for PBP 2a, the target enzyme responsible for methicillin resistance in staphylococci [13].
• beta-Lactam antibiotic-induced release of free endotoxin: in vitro comparison of penicillin-binding protein (PBP) 2-specific imipenem and PBP 3-specific ceftazidime [1].
• Similarly, BM 15766 and Wy-14,643 increased transcription of the PMP68 gene in vitro, whereas PBP gene transcription was increased by Wy-14,643 but not by BM 15766 [10].
• The affinity of BMS-247243 for PBP 2a was >100-fold better than that of methicillin or cefotaxime [13].
• Dietary clofibrate, di-2-(ethylhexyl)phthalate and Wy-14,643, three structurally unrelated proliferators, all increased the mRNA and protein content of PMP68 approx. 2-fold, whereas PBP was induced 8-13-fold [10].

Enzymatic interactions of Dock3

• The pesticides parathion, fonofos, DEF, Mocap and profenofos were oxidized by the reconstituted monooxygenase system to form acetylcholinesterase (AChE) inhibitors [14].

Regulatory relationships of Dock3

• MOCA induces membrane spreading by activating Rac1 [7].

Other interactions of Dock3

• Calsenilin has been identified as a presenilin-binding protein, a transcription factor regulating dynorphin expression, and a beta-subunit of Kv4 channels and could, thus, be a multifunctional protein [15].

Analytical, diagnostic and therapeutic context of Dock3

• Immunofluorescence data indicated that PBP was distributed evenly throughout most of the prostatic acini [8].

References