Activation of mitogen-activated protein kinase by the bradykinin B-2 receptor is independent of receptor phosphorylation and phosphorylation-triggered internalization

Recent evidence suggests that serine/threonine phosphorylation and internal ization of beta(2)-adrenergic receptors play critical roles in signalling t o 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-ac tivated protein kinase by G alpha(q)-coupled bradykinin B-2 receptors. Muta nt B-2 receptors impaired in receptor phosphorylation and internalization a re fully capable to activate mitogen-activated protein kinase. Bradykinin-i nduced long-term effects on mitogenic signalling monitored by measuring the transcriptional activity of Elk1 were identical in cells expressing the wi ldtype or mutant B-2 receptors, Therefore, G protein-coupled bradykinin rec eptors activate the mitogen-activated protein kinase pathway independently of receptor phosphorylation and internalization. (C) 1999 Federation of Eur opean Biochemical Societies.