Activation of mitogen‐activated protein kinase by the bradykinin B2 receptor is independent of receptor phosphorylation and phosphorylation‐triggered internalization

• Published in: FEBS letters 1999-05, Vol.451 (3), p.337-341
• Main Authors: Blaukat, Andree, Pizard, Anne, Rajerison, Rabary M., Alhenc-Gelas, François, Müller-Esterl, Werner, Dikic, Ivan
• Format: Article
• Language: English
• Subjects: B2R, bradykinin B2 receptor; Bradykinin - pharmacology; Bradykinin B2 receptor; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell Line; EGF, epidermal growth factor; Enzyme Activation; ERK2, extracellular-regulated kinase 2; GPCR, G protein-coupled receptor; HA, hemagglutinin; Humans; Internalization; MAP kinase, mitogen-activated protein kinase; MBP, myelin basic protein; Mitogen-activated protein kinase; Mitogenic signalling; Phosphorylation; PMA, phorbol-12-myristate-13-acetate; Receptor, Bradykinin B2; Receptors, Bradykinin - agonists; Receptors, Bradykinin - metabolism; Signal Transduction - drug effects
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00613-4

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 Gαq‐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.