Jun N-terminal protein kinase enhances middle ear mucosal proliferation during bacterial otitis media.

Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity.

Constitutively active Gq impairs gonadotropin-releasing hormone-induced intracellular signaling and luteinizing hormone secretion in LbetaT2 cells.

Chronic GnRH treatment causes homologous desensitization by reducing GnRH receptor and Gq/11 expression and by down-regulating protein kinase C (PKC), cAMP, and calcium-dependent signaling. It also causes heterologous desensitization of other Gq-coupled receptors, but the mechanisms involved remain elusive. In this study, we investigated the effect of constitutive activation of Gq signaling on GnRH-induced signaling and LH secretion.

Methyl scanning: total synthesis of demethylasterriquinone B1 and derivatives for identification of sites of interaction with and isolation of its receptor(s).

The principle of methyl scanning is proposed for determination of the sites of interaction between biologically active small molecules and their macromolecular target(s). It involves the systematic preparation of a family of methylated derivatives of a compound and their biological testing. As a functional assay, the method can identify the regions of a molecule that are important (and unimportant) for biological activity against even unknown targets, and thus provides an excellent complement to structural biology.

Gonadotropin-releasing hormone-desensitized LbetaT2 gonadotrope cells are refractory to acute protein kinase C, cyclic AMP, and calcium-dependent signaling.

Sustained exposure of gonadotropes to GnRH causes a pronounced desensitization of gonadotropin release, but the mechanisms involved are poorly understood. It is known that desensitization is associated with decreased GnRH receptor and Gq/11 levels in alphaT3-1 cells, but it is not known whether downstream signaling is impaired. We have shown previously that chronic stimulation of signaling via expression of an active form of Galphaq causes GnRH resistance in LbetaT2 cells.

Rottlerin inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes by uncoupling mitochondrial oxidative phosphorylation.

There is increasing evidence that protein kinase C (PKC) isoforms modulate insulin-signaling pathways in both positive and negative ways. Recent reports have indicated that the novel PKCdelta mediates some of insulin's actions in muscle and liver cells. Many studies use the specific inhibitor rottlerin to demonstrate the involvement of PKCdelta.

Involvement of both G(q/11) and G(s) proteins in gonadotropin-releasing hormone receptor-mediated signaling in L beta T2 cells.

The hypothalamic hormone gonadotropin-releasing hormone (GnRH) stimulates the synthesis and release of the pituitary gonadotropins. GnRH acts through a plasma membrane receptor that is a member of the G protein-coupled receptor (GPCR) family. These receptors interact with heterotrimeric G proteins to initiate downstream signaling.

Transcriptional activation of the ovine follicle-stimulating hormone-beta gene by gonadotropin-releasing hormone involves multiple signal transduction pathways.

GnRH regulates gonadotrope cells through GnRH receptor activation of the PKC-, MAPK-, and calcium-activated signaling cascades. Due to the paucity of homologous model systems expressing FSHbeta, little is known about the specific mechanisms involved in transcriptional regulation of this gene by GnRH. Previous studies from our laboratory demonstrated that the gonadotrope-derived LbetaT2 cell line expresses FSHbeta mRNA.

GnRH activates ERK1/2 leading to the induction of c-fos and LHbeta protein expression in LbetaT2 cells.

GnRH acts on pituitary gonadotropes to stimulate the synthesis and release of LH and FSH. However, the signaling pathways downstream of the GnRH receptor that mediate these effects are not fully understood. In this paper, we demonstrate that GnRH activates ERK, c-Jun N-terminal kinase, and p38MAPK in the LbetaT2 gonadotrope cell line.

PLC-gamma1 enzyme activity is required for insulin-induced DNA synthesis.

Previously, we had shown that inhibition of PLC activity impaired the ability of insulin to activate ERK in 3T3-L1 adipocytes. In this study, we confirmed that the insulin receptor and PLC-gamma1 are physically associated in hIRcB fibroblasts, insulin stimulates PLC-gamma1 enzyme activity, and inhibition of PLC activity impairs activation of ERK. We subsequently investigated whether PLC-gamma1 is required for insulin-stimulated mitogenesis.