Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, prostaglandin (PG) F2alpha was found to activate mitogen-activated protein (MAP) kinase and MAP kinase kinase (MEK) in cultured rat puerperal uterine myometrial cells. PGF2alpha stimulation also led to an increase in phosphorylation of raf-1, son of sevenless (SOS), and Shc. Furthermore, we examined the mechanism by which PGF2alpha induced MAP kinase phosphorylation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase 1 (betaARK1), which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the PGF2alpha-induced activation of MAP kinase. Ritodrine (1 microM), which is known to relax uterine muscle contraction, attenuated PGF2alpha-induced tyrosine phosphorylation of MAP kinase. Moreover, to examine the role of MAP kinase pathway in uterine contraction, an inhibitor of MEK activity, PD098059, was used. Although MEK inhibitor had no effect on PGF2alpha-induced calcium mobilization, this inhibitor partially inhibited PGF2alpha-induced uterine contraction. These results provide evidence that PGF2alpha stimulates the MAP kinase signaling pathway in cultured rat puerperal uterine myometrial cells through Gbetagamma protein, suggesting that this new pathway may play an important role in the biological action of PGF2alpha on these cells.
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PMID:Role of mitogen-activated protein kinase pathway in prostaglandin F2alpha-induced rat puerperal uterine contraction. 923 56

The regulation of mitogen-activated protein (MAP) kinase by endothelin-1 (ET-1) in cultured rat puerperal uterine myometrial cells was investigated. ET-1 caused the rapid stimulation of MAP kinase activity. ET-1-induced MAP kinase activation is neither extracellular Ca2+- nor intracellular Ca2+-dependent. ET-1 stimulation also led to an increase in phosphorylation of son-of-sevenless (SOS), and transfection of dominant negative SOS attenuated the ET-1-induced MAP kinase activity. Phorbol-12-myristate 13-acetate (PMA) also induced the MAP kinase activity, but pretreatment of the cultured cells with PMA, to down-regulate protein kinase C (PKC), did not abolish the activation of MAP kinase by ET-1. In addition, down-regulation of PKC had no effect on ET-1-induced SOS phosphorylation. Pertussis toxin, which inactivates Gi/Go proteins, blocked the ET-1-induced MAP kinase activation but not the PMA-induced MAP kinase activation. The results suggested that MAP kinase is acutely activated by ET-1 through a pertussis toxin-sensitive G protein and SOS, not through the PMA-sensitive PKC. In addition, although reverse-transcriptase PCR assays detected messenger RNA for both ET- 1 receptor subtypes in cultured rat puerperal uterine myometrial cells, ET-1-induced MAP kinase activity and uterine contraction were blocked by treatment with BQ485, an antagonist selective for an ET type A receptor (but not by BQ788, an ET type B receptor antagonist). Ritodrine, which is known to relax uterine muscle contraction, attenuated ET-1-induced MAP kinase activity. We further examined the role of MAP kinase pathway in uterine contraction using an inhibitor of MEK activity, PD098059. This inhibitor completely inhibited the ET-1-induced MAP kinase activation and partially, but significantly, inhibited the ET-1-induced uterine contraction. These results indicate that ET-1-induced MAP kinase signaling cascade may play an important role in the ET-1-induced uterine contraction.
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PMID:Mitogen-activated protein kinase cascade is involved in endothelin-1-induced rat puerperal uterine contraction. 992 99