Angiotensin II Stimulates Calcium-Dependent Activation of c-Jun N-Terminal Kinase
Thapsigargin
c-jun
DOI:
10.1128/mcb.15.11.6160
Publication Date:
2015-10-09T00:18:10Z
AUTHORS (5)
ABSTRACT
In GN4 rat liver epithelial cells, angiotensin II (Ang II) and other agonists which activate phospholipase C stimulate tyrosine kinase activity in a calcium-dependent, protein (PKC)-independent manner.Since Ang also produces proliferative response these we investigated downstream signaling elements traditionally linked to growth control by kinases.First, II, like epidermal factor (EGF), stimulated AP-1 binding PKC-independent manner.Because increases can reflect induction of c-Jun c-Fos, examined the mitogen-activated (MAP) family members Erk-1 -2 N-terminal (JNK), are known influence c-Fos transcription.Ang MAP (MAPK) but only ϳ50% as effectively EGF; again, effects were independent PKC.Ang produced 50-to 200-fold activation JNK manner.Unlike its smaller effect on MAPK, was approximately four-to sixfold more potent activating than EGF was.Although others had reported lack calcium ionophore-stimulated lymphocytes several cell lines, role cells.The following results suggest that cells is at least partially Ca 2؉ dependent: (i) norepinephrine vasopressin hormones increase inositol 1,4,5-triphosphate JNK; (ii) both thapsigargin, compound an intracellular signal, ionophores dramatic (up 200-fold); (iii) extracellular chelation with ethylene glycol tetraacetic acid (EGTA) inhibited ionophore 1,2-bis-(oaminophenoxy)-ethane-N,N,N,N-tetraacetic tetraacetoxymethyl-ester (BAPTA-AM) or thapsigargin; (iv) pretreatment thapsigargin EGTA, procedure depletes stores.JNK stimulation did not involve calmodulin; neither W-7 nor calmidizolium, concentrations sufficient inhibit /calmodulin-dependent blocked II.In contrast, genistein, -dependent phosphorylation, prevented thapsigargin-induced activation.In summary, stimulates via novel pathway.The inhibition genistein suggests phosphorylation may modulate pathway type-specific manner, particularly readily detectable -regulated kinase.
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