Lysophosphatidylcholine activates mesangial cell PKC and MAP kinase by PLCgamma-1 and tyrosine kinase-Ras pathways.
Although lysophosphatidylcholine (LPC)-mediated cellular responses are attributed to the activation of protein kinase C (PKC), relatively little is known about the upstream signaling mechanisms that regulate the activation of PKC and downstream mitogen-activated protein (MAP) kinase. LPC activated p42 MAP kinase and PKC in mesangial cells. LPC-mediated MAP kinase activation was inhibited (but not completely) by PKC inhibition, suggesting additional signaling events. LPC stimulated protein tyrosine kinase (PTK) activity and induced Ras-GTP binding. LPC-induced MAP kinase activity was blocked by the PTK inhibitor genistein. Because LPC increased PTK activity, we examined the involvement of phospholipase Cgamma-1 (PLCgamma-1) as a key participant in LPC-induced PKC activation. LPC stimulated the phosphorylation of PLCgamma-1. PTK inhibitors suppressed LPC-induced PKC activity, whereas the same had no effect on phorbol 12-myristate 13-acetate-mediated PKC activity. Other lysophospholipids [e.g., lysophosphatidylinositol and lysophosphatidic acid (LPA)] also induced MAP kinase activity, and only LPA-induced MAP kinase activation was sensitive to pertussis toxin. These results indicate that LPC-mediated PKC activation may be regulated by PTK-dependent activation of PLCgamma-1, and both PKC and PTK-Ras pathways are involved in LPC-mediated downstream MAP kinase activation.
Bassa
B V
BV
Nephrology Section, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Roh
D D
DD
Vaziri
N D
ND
Kirschenbaum
M A
MA
Kamanna
V S
VS
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation; D005920:Glomerular Mesangium / Q000187:drug effects / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D051379:Mice; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000502:physiology; D018631:ras Proteins / Q000502:physiology
D007527:Isoenzymes; D008244:Lysophosphatidylcholines; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D018631:ras Proteins