Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.12.2 (
MEK
)
18,161
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Vascular endothelial growth factor (VEGF) stimulated a time- and concentration-dependent increase in PGI2 synthesis in human umbilical vein endothelial cells with a mean maximum increase of 2-fold above basal levels at 25 ng/ml after 60 min. VEGF also rapidly stimulated the release of arachidonic acid and phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). The
VEGF-related factor
, placenta growth factor (PIGF), had little effect on PGI2 synthesis, arachidonic acid release or cPLA2 activation. PD98059, a selective inhibitor of
MAP kinase kinase
, caused complete inhibition of VEGF-stimulated MAP kinase activity, PGI2 synthesis and cPLA2 gel retardation, but had no effect on VEGF-induced vWF secretion. These findings provide the first evidence that VEGF can stimulate PGI2 synthesis via cPLA2-mediated arachidonic acid release and indicate that VEGF stimulation of this biosynthetic pathway may occur, at least in part, via activation of p42/p44 MAP kinases.
...
PMID:Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase. 945 May 44
Interactions between tumors and host tissues play essential roles in tumor-induced systemic wasting and cancer cachexia, including muscle wasting and lipid loss. However, the pathogenic molecular mechanisms of wasting are still poorly understood. Using a fly model of tumor-induced organ wasting, we observed aberrant
MEK
activation in both tumors and host tissues of flies bearing gut-yki
3SA
tumors. We found that host
MEK
activation results in muscle wasting and lipid loss, while tumor
MEK
activation is required for tumor growth. Strikingly, host
MEK
suppression alone is sufficient to abolish the wasting phenotypes without affecting tumor growth. We further uncovered that yki
3SA
tumors produce the vein (vn) ligand to trigger autonomous Egfr/
MEK
-induced tumor growth and produce the PDGF- and
VEGF-related factor
1 (Pvf1) ligand to non-autonomously activate host Pvr/
MEK
signaling and wasting. Altogether, our results demonstrate the essential roles and molecular mechanisms of differential
MEK
activation in tumor-induced host wasting.
...
PMID:Tumor-Derived Ligands Trigger Tumor Growth and Host Wasting via Differential MEK Activation. 3063 55
