Activation of mitogen-activated protein kinase by the bradykinin B2receptor is independent of receptor phosphorylation and phosphorylation-triggered internalization

Abstract

Recent evidence suggests that serine/threonine phosphorylation and internalization of β₂‐adrenergic receptors play critical roles in signalling to the mitogen‐activated protein kinase cascade. To investigate whether this represents a general mechanism employed by G protein‐coupled receptors, we studied the requirement of these processes in the activation of mitogen‐activated protein kinase by Gα_q‐coupled bradykinin B₂ receptors. Mutant B₂ receptors impaired in receptor phosphorylation and internalization are fully capable to activate mitogen‐activated protein kinase. Bradykinin‐induced long‐term effects on mitogenic signalling monitored by measuring the transcriptional activity of Elk1 were identical in cells expressing the wild‐type or mutant B₂ receptors. Therefore, G protein‐coupled bradykinin receptors activate the mitogen‐activated protein kinase pathway independently of receptor phosphorylation and internalization.