Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to investigate the role of D(4) dopamine receptors in regulating the Akt/nuclear factor-kappa B (NF-kappa B) and extracellular signal-regulated kinase (ERK) signaling pathways. The D(4) dopamine receptor agonist PD168077 induced time- and dose-dependent activation of Akt and ERK in D(4)MN9D cells that stably express D(4) dopamine receptors. Maximal Akt and ERK stimulation was achieved at 1 microM PD168077. The agonist-mediated stimulations of Akt and ERK were abolished when cells were preincubated with 50 ng/ml PTX or with 1 microM L745,870, a D(4) dopamine receptor antagonist, indicating that activation of the Akt or ERK pathways is mediated by D(4) dopamine receptors and require a pertussis toxin-sensitive G protein. We also detected a time- and dose-dependent activation of NF-kappa B. Activation of NF-kappa B by 1 microM PD168077 was attenuated in D(4)MN9D cells that were transfected with a kinase-deficient Akt but not in cells transfected with a dominant negative Ras (N17Ras), suggesting that NF-kappa B activation requires Akt but is independent of Ras. In contrast, the transfection of N17Ras into D(4)MN9D cells blunted D(4) dopamine receptor-mediated ERK activation, indicating a Ras-dependent mechanism. Moreover, PP2 (20 nM), an inhibitor of Src, blocked D(4) receptor-mediated SHC phosphorylation and ERK activation. In contrast, transfection of a kinase-dead Akt did not alter D(4) receptor-stimulated ERK. However, PP2 and the mitogen activated protein kinase kinase inhibitor PD98059 did not change D(4) receptor-mediated Akt/NF-kappa B activation. All these indicate that distinct mechanisms mediate ERK and Akt/NF-kappa B activation by D(4) dopamine receptor stimulation. We also demonstrated that D(4) receptor-stimulated cell proliferation is mediated by the Src/SHC/Ras/ERK pathway.
 ...
PMID:D(4) dopamine receptor differentially regulates Akt/nuclear factor-kappa b and extracellular signal-regulated kinase pathways in D(4)MN9D cells. 1156 49