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Apelin (65–77) Activates Extracellular Signal-Regulated Kinases via a PTX-Sensitive G Protein

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Abstract

We report here that apelin (65–77) induces activation of extracellular-regulated kinases (ERKs) in Chinese hamster ovary (CHO) cells expressing the msr/apj receptor. This concentration-dependent activation was transient, peaking at 5 min. Pretreatment of CHO cells with pertussis toxin fully abrogated ERK phosphorylation, whereas overexpression of the β-adrenergic receptor kinase-1 C-terminal fragment did not alter ERK activation. Transfection with a dominant-negative mutant of Ras was without effect on ERK activation, whereas an inhibitor of many protein kinase C isoforms, GF109203X, strongly decreased it. These results demonstrate that stimulation of the murine msr/apj receptor promotes ERK activation via the α subunit of a pertussis toxin-sensitive protein in a Ras-independent pathway.

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    Abbreviations used: ARK, adrenergic receptor kinase; cAMP, cyclic adenosine monophosphate; CHO, Chinese hamster ovary; DG, diacylglycerol; ERK, extracellular-regulated kinase; GPCR, G protein-coupled receptor; IP3, inositol 1,4,5-triphosphate; MAPK, mitogen-activated protein kinase; MEK, MAP kinase kinase; PI, phosphatidylinositol; PKA, protein kinase A; PKC, protein kinase C; PTX, pertussis toxin.

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