Sphingosylphosphorylcholine stimulates mitogen-activated protein kinase via a Ca2+-dependent pathway
- 1 November 1998
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Cell Physiology
- Vol. 275 (5) , C1255-C1263
- https://doi.org/10.1152/ajpcell.1998.275.5.c1255
Abstract
In cultured porcine aortic smooth muscle cells, sphingosylphosphorylcholine (SPC), ATP, or bradykinin (BK) induced a rapid dose-dependent increase in the cytosolic Ca2+concentration ([Ca2+]i) and also stimulated inositol 1,4,5-trisphosphate (IP3) generation. Pretreatment of cells with pertussis toxin blocked the SPC-induced IP3generation and [Ca2+]iincrease but had no effect on the action of ATP or BK. In addition, SPC stimulated the mitogen-activated protein kinase (MAPK) and increased DNA synthesis, whereas neither ATP nor BK produced such effects. Both the SPC-induced MAPK activation and DNA synthesis were pertussis toxin sensitive. SPC-induced MAPK activation was blocked by treatment of cells with the phospholipase C inhibitor, U-73122, or the intracellular Ca2+-ATPase inhibitor, thapsigargin, but not by removal of extracellular Ca2+. Lysophosphatidic acid induced cellular responses similar to SPC in a pertussis toxin-sensitive manner in terms of [Ca2+]iincrease, IP3generation, MAPK activation, and DNA synthesis. Platelet-derived growth factor (PDGF) also induced a [Ca2+]iincrease, MAPK activation, and DNA synthesis in the same cells; however, the PDGF-induced MAPK activation was not sensitive to pertussis toxin and changes in [Ca2+]i. SPC-induced MAPK activation was inhibited by pretreatment of cells with staurosporine, W-7, or calmidazolium. Our results suggest that, in porcine aortic smooth muscle cells, MAPK is not activated by the increase in [Ca2+]iunless a pertussis toxin-sensitive G protein is simultaneously stimulated, indicating the role of Ca2+in pertussis toxin-sensitive G protein-mediated MAPK activation.Keywords
This publication has 26 references indexed in Scilit:
- Protein Kinase C-ζ Mediates Angiotensin II Activation of ERK1/2 in Vascular Smooth Muscle CellsPublished by Elsevier ,1997
- A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activationNature, 1996
- Antagonistic Effect of Na+ and Mg2+ on P2z Purinoceptor‐Associated Pores in Dibutyryl Cyclic AMP‐Differentiated NG108‐15 CellsJournal of Neurochemistry, 1996
- Identification of an Essential Signaling Cascade for Mitogen-activated Protein Kinase Activation by Angiotensin II in Cultured Rat Vascular Smooth Muscle CellsJournal of Biological Chemistry, 1996
- Pertussis Toxin Inhibits Phospholipase C Activation and Ca2+ Mobilization by Sphingosylphosphorylcholine and Galactosylsphingosine in HL60 Leukemia CellsPublished by Elsevier ,1995
- Sphingosylphosphorylcholine Activation of Mitogen-activated Protein Kinase in Swiss 3T3 Cells Requires Protein Kinase C and a Pertussis Toxin-sensitive G ProteinJournal of Biological Chemistry, 1995
- α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, but Not N-Methyl-D-aspartate, Activates Mitogen-activated Protein Kinase through G-protein βγ Subunits in Rat Cortical NeuronsPublished by Elsevier ,1995
- Lysophosphatidic Acid, a Multifunctional Phospholipid MessengerJournal of Biological Chemistry, 1995
- Ras-dependent activation of MAP kinase pathway mediated by G-protein βγ subunitsNature, 1994
- Signaling pathways for sphingosylphosphorylcholine-mediated mitogenesis in Swiss 3T3 fibroblasts.The Journal of cell biology, 1993