Role for phospholipase D in receptor-mediated endocytosis.
In response to epidermal growth factor (EGF), the EGF receptor is endocytosed and degraded. A substantial lag period exists between endocytosis and degradation, suggesting that endocytosis is more than a simple negative feedback. Phospholipase D (PLD), which has been implicated in vesicle formation in the Golgi, is activated in response to EGF and other growth factors. We report here that EGF receptor endocytosis is dependent upon PLD and the PLD1 regulators, protein kinase C alpha and RalA. EGF-induced receptor degradation is accelerated by overexpression of either wild-type PLD1 or PLD2 and retarded by overexpression of catalytically inactive mutants of either PLD1 or PLD2. EGF-induced activation of mitogen-activated protein kinase, which is dependent upon receptor endocytosis, is also dependent upon PLD. These data suggest a role for PLD in signaling that facilitates receptor endocytosis.
Shen
Y
Y
Department of Biological Sciences, Hunter College of The City University of New York, New York, New York 10021, USA.
Xu
L
L
Foster
D A
DA
D020001:1-Butanol / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000440:Butanols / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051571:Protein Kinase C-alpha; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D020725:ral GTP-Binding Proteins
D000440:Butanols; D007527:Isoenzymes; C040507:isobutyl alcohol; D004815:Epidermal Growth Factor; D020001:1-Butanol; D066246:ErbB Receptors; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D020928:Mitogen-Activated Protein Kinases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D020558:GTP Phosphohydrolases; C492197:Rala protein, rat; D020725:ral GTP-Binding Proteins