Dissociation of functional roles of dynamin in receptor-mediated endocytosis and mitogenic signal transduction.
Dynamin plays a critical role in the membrane fission mechanism that mediates regulated endocytosis of many G protein-coupled receptors. In addition, dynamin is required for ligand-induced activation of mitogen-activated protein kinase by certain receptors, raising a general question about the role of dynamin in mitogenic signal transduction. Here we report that endocytosis of mu and delta opioid receptors is not required for efficient ligand-induced activation of mitogen-activated protein kinase. Nevertheless, mitogenic signaling mediated by these receptors is specifically dynamin-dependent. Thus a functional role of dynamin in mitogenic signaling can be dissociated from its role in receptor-mediated endocytosis, suggesting a previously unidentified and distinct role of dynamin in signal transduction by certain G protein-coupled receptors.
Whistler
J L
JL
Department of Psychiatry, Program in Cell Biology, University of California, San Francisco, California 94143-0984, USA.
von Zastrow
M
M
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D034281:Dynamins; D004705:Endocytosis; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005048:Etorphine / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D009020:Morphine / Q000494:pharmacology; D010766:Phosphorylation; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
D004745:Enkephalins; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005048:Etorphine; D009020:Morphine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D034281:Dynamins