title: Phospholipase D2 activation by p38 MAP kinase is involved in neurite outgrowth.
abstract: p38 mitogen-activated protein (MAP) kinase plays an important role in neurite outgrowth. However, the underlying molecular mechanism(s) remains unclear. Here, we demonstrate that phospholipase D2 (PLD2) mediates p38 signaling in neurite outgrowth. Stimulation of rat pheochromocytoma PC12 cells with nerve growth factor activated PLD2 and augmented neurite outgrowth, both of which were inhibited by pharmacological suppression of p38. Overexpression of constitutively active MAP kinase kinase 6 (MKK6-CA) activated coexpressed PLD2 in PC12 and mouse neuroblastoma N1E-115 cells. Overexpression of wild-type PLD2 in these cells strongly augmented the neurite outgrowth induced by MKK6-CA, whereas lipase-deficient PLD2 suppressed it. These findings provide evidence that PLD2 functions as a downstream molecule of p38 in the neurite outgrowth signaling cascade.
authors: Department of Physiological Chemistry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors: Hiroshi
authors: H
authors: Watanabe
authors: Tsunaki
authors: T
authors: Hongu
authors: Masakazu
authors: M
authors: Yamazaki
authors: Yasunori
authors: Y
authors: Kanaho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000201:enzymology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D016716:PC12 Cells; D010739:Phospholipase D / Q000096:biosynthesis*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D020932:Nerve Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C105606:phospholipase D2; D010739:Phospholipase D