Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MAP kinase pathway has been shown to be active in many growth factor signaling systems, including that of prolactin (PRL). In our studies, the main objective was to examine the possible involvement of MEK kinases (Map/Erk kinase kinases) in PRL-stimulated mitogenic and lactogenic processes. We used the MEK kinase inhibitor PD 098059 to block MEK kinase activation in the Nb2 cell line and mammary gland explants derived from 12- to 14-day pregnancy mice. PD 098059 attenuated PRL-induced Nb2 cell mitogenesis at 10 microM and a maximum inhibition was observed at 100 microM. In cultured mammary tissues, PD 098059 at 100 microM had no effect on the PRL stimulation of lipid, casein and lactose synthesis and iodide uptake. Further, the growth-inhibitory effect of PD 098059 on Nb2 cells was ameliorated when the drug was removed from the culture medium, indicating that PD 098059 acts in a reversible manner. When MEK1 was immunoprecipitated from PD 098059 and/or PRL treated Nb2 cells, PRL-stimulated MEK1 kinase activity was directly inhibited by PD 098059 at concentrations employed in the culture experiments. PRL has no effect on the tyrosyl phosphorylation of MAP kinases in cultured mammary tissues derived from pregnant mice, whereas earlier we found that PRL stimulates the tyrosyl phosphorylation of all four MAP kinases in Nb2 cells. The results suggest that the MAP kinase pathway plays an important role in the PRL stimulation of Nb2 cell mitogenesis but is not involved in the PRL stimulation of milk product synthesis.
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PMID:The MEK inhibitor PD 098059 inhibits prolactin-induced Nb2 cell mitogenesis but not milk product synthesis in cultured mouse mammary tissues. 982 84

Bivalent lectins as bridging molecules between cells or cell surface lectins as docking points are involved in mediation of cell adhesion by specific recognition of suitable glycoconjugates on an opposing surface. The initial contact formation by a lectin can lead to intracellular post-binding events which effect stable cell association even in the presence of the haptenic sugar. To delineate the participation of intracellular signaling pathways in the cascade of reactions to establish firm association, reagents with proven inhibitory capacity on certain biochemical targets provide suitable tools. Using this approach with rat thymocytes and the galactoside-binding lectin from mistletoe (Viscum album L. agglutinin, VAA) as a model, a panel of 27 inhibitors with impact on e.g. several types of kinases, tyrosine phosphatases, NO synthases, G proteins, enzymes of arachidonate and cyclic nucleotide metabolism and calmodulin was systematically tested with respect to their capacity to impair the formation of lactose-resistant cell aggregates. In addition to the recently reported effectiveness of N-ethylmaleimide, nordihydroguaiaretic acid, and trifluoperazine the agents diacylglycerol kinase inhibitor II, emodin, D609, DPI, KT5720, KT5926, MK-886, bisindolylmaleimide I, and (+/-)methoxyverapamil were able to reduce aggregate stability in the presence of the haptenic sugar. Thus, various types of kinases including p561lck tyrosine kinase, lipoxygenases, phosphatidylcholine-specific phospholipase C as well as calmodulin and Ca(2+)-currents, but not modulators of the metabolism of cyclic nucleotides, NO synthases, MAP kinases, tyrosine phosphatases and phospholipase A (preferentially group II) and C can play a role in eliciting contact stability. More than one principal signaling pathway appears to be linked to the measurable parameter, since inhibitory substances show additive properties in co-incubation assays and differentially affect two lectin-elicited cellular activities, i.e. intracellular movement of Ca(2+)-ions and H2O2-generation, which can accompany cell adhesion and aggregation. Pronounced differences in the extent of modulation of H2O2-generation in human neutrophils by the same set of substances emphasizes that general conclusions on the post-binding effects for a certain lectin in different cell types are definitely precluded. In aggregate, the approach to employ inhibitors with target selectivity intimates an involvement of protein kinases A, C, Ca2+/calmodulin-dependent protein kinase II, p56lck tyrosine kinase, leukotrienes and/or hydroxyeicosatetraenoic acids, phosphatidylcholine-specific phospholipase C and Ca(2+)-fluxes in events following initial binding of a galactoside-specific plant lectin to rat thymocytes which establish firm cell contacts.
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PMID:Dissection of the impact of various intracellular signaling pathways on stable cell aggregate formation of rat thymocytes after initial lectin-dependent cell association of using a plant lectin as model and target-selective inhibitors. 1048 33

Milk yield, milk ingredients, health and other, production-related parameters of subclinically infected, Mycobacterium avium ssp. paratuberculosis (MAP-) shedding (positive faecal PCR, n = 20) and non-shedding (negative faecal PCR, n = 10) dairy cows were compared in the period from 10 days prepartum to 120 days postpartum. Body condition, rumen fill and faeces scores were lower in the MAP-shedding cows. There was no significant difference in plasma or urine metabolic parameters between the groups. Milk yield and lactose content tended to be lower (P = 0.074 and 0.077, respectively), somatic cell count tended to be higher (P = 0.097), while milk fat content was significantly higher (P = 0.006) in MAP-shedding cows than in the controls. Milk protein content did not differ between the groups. All other health and production parameters [number of reproductive tract treatments, number of udder treatments, number of artificial inseminations (AIs), calving interval, and service period] were significantly better in the control group. It is concluded that MAP infection, even in a subclinical form, has a significant impact on some production and health parameters of dairy cows.
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PMID:Effects of subclinical Mycobacterium avium ssp. paratuberculosis infection on some physiological parameters, health status and production in dairy cows. 2765 27