title: α1 -Adrenergic receptor-induced cytoskeletal organization and cell motility in CCL39 fibroblasts requires phospholipase D1.
abstract: The role of phospholipase D (PLD) in cytoskeletal reorganization, ERK activation, and migration is well established. Both isoforms of PLD (PLD1 and PLD2) can independently activate stress fiber formation and increase ERK phosphorylation. However, the isoform's specificity, upstream activators, and downstream targets of PLD that coordinate this process are less well understood. This study explores the role of α(1) -adrenergic receptor stimulation and its effect on PLD activity. We demonstrate that PLD1 activators, RhoA, and PKCα are critical for stress fiber formation and ERK activation, and enhance the production of phosphatidic acid (PA) upon phenylephrine addition. Ectopic expression of dominant negative PLD1 and not PLD2 blocks ERK activation, inhibits stress fiber formation, and reduces cell motility in CCL39 fibroblasts. Furthermore, we demonstrate the mechanism for PLD1 activation of ERK involves Ras. This work indicates that PLD1 plays a novel role mediating growth factor and cell motility events in α(1) -adrenergic receptor-activated cells.
authors.affiliation: Departments of Biosciences and Chemistry, Minnesota State University Moorhead, Moorhead, Minnesota 56563, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wallert
authors.forename: A
authors.initials: A
authors.lastname: McCoy
authors.forename: J
authors.initials: J
authors.lastname: Voog
authors.forename: D
authors.initials: D
authors.lastname: Rastedt
authors.forename: J
authors.initials: J
authors.lastname: Taves-Patterson
authors.forename: N
authors.initials: N
authors.lastname: Korpi-Steiner
authors.forename: J
authors.initials: J
authors.lastname: Canine
authors.forename: T
authors.initials: T
authors.lastname: Ngyuen
authors.forename: C
authors.initials: C
authors.lastname: Nguyen
authors.forename: J
authors.initials: J
authors.lastname: Provost
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D010712:Phosphatidic Acids; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D051571:Protein Kinase C-alpha; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein