Activation of mitogen-activated protein kinase by the bradykinin B2 receptor is independent of receptor phosphorylation and phosphorylation-triggered internalization.
Recent evidence suggests that serine/threonine phosphorylation and internalization of beta2-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 G alpha(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.
Blaukat
A
A
Ludwig Institute for Cancer Research, Uppsala, Sweden.
Pizard
A
A
Rajerison
R M
RM
Alhenc-Gelas
F
F
Müller-Esterl
W
W
Dikic
I
I
D001920:Bradykinin / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D010766:Phosphorylation; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001920:Bradykinin