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)

Lysyl oxidase (LOX) down-regulation induced an oncogenic phenotype in NRK-49F. This event was accompanied by a constitutive activation of ras oncogene and down-regulation of PDGF beta receptor, among other important phenotypic and molecular modifications. In the present paper we show that ras activation is not accompanied by a constitutive activation of the MAP kinases as expected. Surprisingly, even if MAPK-independent, ras activation was accompanied by a constitutive Ser(63) and Ser(73) phosphorylation of c-jun, a further downstream target of ras. Although rare, this ras alternative pathway has been described. Since ras alone is seldom able to trigger cell transformation and the transformed phenotype showed clearly an abnormal adhesion pattern, we investigated the main molecules involved in cell-cell adhesion. In fact, we found that beta-catenin was up-regulated, escaping the glycogen synthase kinase-3 beta (GSK-3 beta) control, through unclear mechanisms. Its nuclear accumulation was accompanied by an up-regulation of cyclin D1, as classically described in the activation of the Wnt/beta-catenin signal pathway. We believe that the resulting up-regulation of cyclin D1 acted in synergy with ras to induce the cell transformation.
 ...
PMID:Altered adhesion features and signal transduction in NRK-49F cells transformed by down-regulation of lysyl oxidase. 1268 40

Dehydroepiandrosterone (DHEA) is synthesized in the brain, but whether DHEA is involved in modulating neuronal cell survival is not yet fully understood. Herein we show that when deprived of trophic support, GT1-7 hypothalamic neurons undergo apoptosis following exposure to DHEA, as demonstrated both by morphological and biochemical criteria. This proapoptotic effect appeared to be specific to DHEA itself, and not through conversion of DHEA to other steroids such as androgen or estrogen. Importantly, we determined that IGF-I protects GT1-7 neurons from DHEA-induced cell death. DHEA-induced apoptosis was associated with increased activation of caspase 3 and decreased PARP, which were both attenuated with addition of IGF-I. Addition of DHEA prevented phosphorylation of both Akt and glycogen synthase kinase-3 beta (GSK-3beta), downstream effector molecules of the phosphatidylinositol 3-kinase (PI3K) pathway. Further IGF-I was able to sustain Akt activity and thus preventing GSK-3beta activation in the presence of DHEA. On the other hand, the MAP kinases, ERK, p38, and JNK, were not affected by DHEA. These findings suggest that in GT1-7 hypothalamic neurons, DHEA acts detrimentally to induce cell death and IGF-I is able to rescue the neurons by preserving the activity of Akt, and therefore maintaining the proapoptotic kinase GSK-3beta, in a phosphorylated catalytically inactive state.
 ...
PMID:IGF-I signaling prevents dehydroepiandrosterone (DHEA)-induced apoptosis in hypothalamic neurons. 1506 51