Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphoinositide 3-kinase or Akt, in Chinese hamster ovary cells.
Available evidence suggests the involvement of phospholipase D (PLD) in cell proliferation and survival. Phosphoinositide 3-kinase (PI 3-kinase)/Akt and extracellular signal-regulated kinases (ERKs) are signalling molecules that have essential roles in cell proliferation and survival. We previously demonstrated that sphingosine 1-phosphate (S1P)-induced PLD activation via the G-protein-coupled receptor endothelial differentiation gene (EDG) 3/S1P(3) was involved in S1P-induced stimulation of PI 3-kinase and Akt. In the present study, we examined the involvement of two PLD isozymes, PLD1 and PLD2, in insulin-like growth factor (IGF)-I receptor tyrosine kinase-mediated stimulation of PI 3-kinase/Akt and ERKs. IGF-I and to a lesser degree S1P stimulated PI 3-kinase activity in Chinese hamster ovary cells overexpressing EDG3/S1P(3). IGF-I-induced ERK phosphorylation was suppressed by butan-1-ol, but not butan-2-ol, whereas no effect of butanol was observed in IGF-I-induced Akt activation in S1P(3)-overexpressing Chinese hamster ovary cells. Overexpression of wild-type PLD1 and PLD2 substantially potentiated S1P-, but not IGF-I-, induced activation of PI 3-kinase and Akt, whereas overexpression of the catalytically inactive mutant of PLD1 or PLD2 did not affect the responses to either agonist. On the other hand, overexpression of wild-type PLD1 and PLD2 potentiated IGF-I- and, to much smaller extents, S1P-induced ERK stimulation. ERK activation by IGF-I as well as S1P was dependent on Ras, but Akt activation by IGF-I was not dependent on Ras. These results suggest that PLDs are involved in growth factor regulation of at least two signalling pathways, PI 3-kinase/Akt and ERKs, depending on the class of cell-surface receptors.
Banno
Yoshiko
Y
Department of Biochemistry, Gifu University School of Medicine, Tsukasamachi-40, Gifu 500-8705, Japan. banno@cc.gifu-u.ac.jp
Takuwa
Yoh
Y
Yamada
Momoko
M
Takuwa
Noriko
N
Ohguchi
Kenji
K
Hara
Akira
A
Nozawa
Yoshinori
Y
D000818:Animals; D000440:Butanols / Q000737:chemistry / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism*; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008246:Lysophospholipids; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D000440:Butanols; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D007527:Isoenzymes; D008246:Lysophospholipids; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D010739:Phospholipase D; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1; D013110:Sphingosine; D018631:ras Proteins; C060506:sphingosine 1-phosphate