Disease relevance of Map3k12

• However, PK-treated spirochetes fluoresced intensely after incubation with antibodies to OspA or OspB in the presence of detergent, confirming the existence of large amounts of subsurface Osp antigens [1].
• In this study, we first detected the activation pattern of JNK signaling including mixed lineage kinase (MLK)3, mitogen-activated protein kinase kinase (MKK)7 and JNK3 in hippocampal CA1 and CA3/DG regions at various time points after 15 min of ischemia [2].
• Mechanism of inhibition of mast cell anaphylaxis by P. kurroa-extract (PK) treatment in rats was investigated [3].

High impact information on Map3k12

• Here we report that the introduction of Ca2+/CaM-dependent PK II, autoactivated by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline [4].
• We also show that introduction of a selective peptidergic inhibitor of Ca2+/CaM-dependent PK II inhibits the initial rate of induced glutamate release [4].
• The results strongly suggest that the Ca(2+)-dependent inhibition of PLA2 activity observed in intact nerve endings was produced by activation of the multifunctional Ca2+/CaM-dependent PK II [5].
• In B cells from dispersed rat islet of Langerhans we have identified an inward rectifying voltage-independent K+ channel whose behavior parallels the metabolically regulated potassium permeability (PK) found in tracer flux and microelectrode recording studies [6].
• In our present results, ischemic preconditioning could not only inhibit activations of mixed lineage kinase 3, JNK1/2, and c-Jun but also enhanced activation of Akt1 [7].

Biological context of Map3k12

• To determine the generality and functional significance of this response, we have examined c-jun phosphorylation and the effect on cell death of a novel mixed lineage kinase inhibitor, CEP11004, in the 6-hydroxydopamine model of induced apoptotic death in dopamine neurons [8].
• The activity of the eukaryotic elongation factor 2 (eEF-2)-specific Ca(2+)- and calmodulin-dependent protein kinase III (CaM PK III) is regulated by phosphorylation [9].
• In contrast, neither the JNK inhibitor SP600125 nor the mixed lineage kinase inhibitor CEP-1347 prevented cytosine arabinoside-induced neuronal death, demonstrating that the JNK pathway was not necessary for DNA damage-induced neuronal apoptosis [10].
• The PK MLTF-like site consists of two imperfect CACGTG motifs, the core binding site for a family of transcription factors related to c-myc [11].
• SPRK (also called PTK-1 and MLK-3), a member of the mixed lineage kinase subfamily of (Ser/Thr) protein kinases, encodes an amino-terminal SH3 domain followed by a kinase catalytic domain, two leucine zippers interrupted by a short spacer, a Rac/Cdc42 binding domain, and a long carboxyl-terminal proline-rich region [12].

Anatomical context of Map3k12

• The RSV-induced membrane depolarization is shown to be due to a severalfold increase in the cation permeability ratio (PNa/PK) of the plasma membrane [13].
• Artocarpol A stimulation of superoxide anion generation in neutrophils involved the activation of PLC, PKC and p38 mitogen-activated PK signaling pathways [14].
• Neuronally differentiated PC12 cells and primary murine hippocampal cultures transfected with an expression vector for ICP10 PK were protected from cell death resulting from growth factor withdrawal [15].
• In addition, such MLK inhibition did not prevent androgen replacement induced proliferative regrowth of the prostate epithelium in castrated animals [16].
• CONCLUSIONS: Signaling through the MLK family is not involved in either the androgen-induced proliferation or the androgen ablation-induced apoptosis of prostatic epithelial cell in the rat [16].

Associations of Map3k12 with chemical compounds

• Substitution or inversion of the PK HNF-4 site abrogated the response to glucose and also significantly suppressed the promoter activity under non-inducing conditions [17].
• An exogenous ADP-consuming system consisting of pyruvate kinase (PK; 20-40 units/ml) and phosphoenolpyruvate (PEP; 5 mM), totally suppressed respiration activated by exogenous ADP, but the respiration maintained by endogenous ADP was not suppressed by more than 20-40% [18].
• With the use of this method, Ca2+-calmodulin (CAM)-, Ca2+/phospholipid (PK C)-, cyclic GMP (cGMP)-, and cyclic AMP (cAMP)-dependent protein kinases were detected [19].
• Previously, we showed that myosin II heavy chains bind to phosphatidylserine (PS) liposomes via their COOH terminal regions and that protein kinase C (PK C) phosphorylates the PS-bound heavy chains [Murakami et al. (1994) J. Biol. Chem. 269, 16082-16090] [20].
• These results show that the phosphorylation state of a 37 kDa membrane protein parallels the modulation of insulin release induced by TPA and clomiphene and support a role for PK C in the insulin-secretory mechanism [21].

Physical interactions of Map3k12

• Mixed-lineage kinase 2-SH3 domain binds dynamin and greatly enhances activation of GTPase by phospholipid [22].

Other interactions of Map3k12

• Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival [23].
• Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons [24].

Analytical, diagnostic and therapeutic context of Map3k12

• Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts [25].
• When we attempted to separate PK II from other hepatic cytosol proteins by DEAE-cellulose chromatography, we observed that GTP caused little stimulation of [3H]cAMP binding in an eluate fraction (110 to 170 mmol/L KCI), which was rich in PK II but did stimulate cAMP binding to the 210 to 325 mmol/L KCI fraction, which also contains PK II [26].
• Micropuncture results showed that at comparable PK levels epinephrine had no direct effect on K secretion by the distal tubule but indirectly inhibited K secretion in this nephron segment by reducing PK [27].

References