scholarly journals Sphingosine 1-phosphate rapidly activates the mitogen-activated protein kinase pathway by a G protein-dependent mechanism

1995 ◽  
Vol 270 (19) ◽  
pp. 11484-11488 ◽  
Author(s):  
J Wu ◽  
S Spiegel ◽  
TW Sturgill
1996 ◽  
Vol 271 (3) ◽  
pp. 1266-1269 ◽  
Author(s):  
Tim van Biesen ◽  
Brian E. Hawes ◽  
John R. Raymond ◽  
Louis M. Luttrell ◽  
Walter J. Koch ◽  
...  

1999 ◽  
Vol 190 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Eva E. Prieschl ◽  
Robert Csonga ◽  
Veronica Novotny ◽  
Gary E. Kikuchi ◽  
Thomas Baumruker

Over the last few years, sphingolipids have been identified as potent second messenger molecules modulating cell growth and activation. A newly emerging facet to this class of lipids suggests a picture where the balance between two counterregulatory lipids (as shown in the particular example of ceramide and sphingosine-1-phosphate in T lymphocyte apoptosis) determines the cell fate by setting the stage for various protein signaling cascades. Here, we provide a further example of such a decisive balance composed of the two lipids sphingosine and sphingosine-1-phosphate that determines the allergic responsiveness of mast cells. High intracellular concentrations of sphingosine act as a potent inhibitor of the immunoglobulin (Ig)E plus antigen–mediated leukotriene synthesis and cytokine production by preventing activation of the mitogen-activated protein kinase pathway. In contrast, high intracellular levels of sphingosine-1-phosphate, also secreted by allergically stimulated mast cells, activate the mitogen-activated protein kinase pathway, resulting in hexosaminidase and leukotriene release, or in combination with ionomycin, give cytokine production. Equivalent high concentrations of sphingosine-1-phosphate are dominant over sphingosine as they counteract its inhibitory potential. Therefore, it might be inferred that sphingosine-kinase is pivotal to the activation of signaling cascades initiated at the Fc∈ receptor I by modulating the balance of the counterregulatory lipids.


Reproduction ◽  
2000 ◽  
pp. 377-383 ◽  
Author(s):  
L Leonardsen ◽  
A Wiersma ◽  
M Baltsen ◽  
AG Byskov ◽  
CY Andersen

The mitogen-activated protein kinase-dependent and the cAMP-protein kinase A-dependent signal transduction pathways were studied in cultured mouse oocytes during induced and spontaneous meiotic maturation. The role of the mitogen-activated protein kinase pathway was assessed using PD98059, which specifically inhibits mitogen-activated protein kinase 1 and 2 (that is, MEK1 and MEK2), which activates mitogen-activated protein kinase. The cAMP-dependent protein kinase was studied by treating oocytes with the protein kinase A inhibitor rp-cAMP. Inhibition of the mitogen-activated protein kinase pathway by PD98059 (25 micromol l(-1)) selectively inhibited the stimulatory effect on meiotic maturation by FSH and meiosis-activating sterol (that is, 4,4-dimethyl-5alpha-cholest-8,14, 24-triene-3beta-ol) in the presence of 4 mmol hypoxanthine l(-1), whereas spontaneous maturation in the absence of hypoxanthine was unaffected. This finding indicates that different signal transduction mechanisms are involved in induced and spontaneous maturation. The protein kinase A inhibitor rp-cAMP induced meiotic maturation in the presence of 4 mmol hypoxanthine l(-1), an effect that was additive to the maturation-promoting effect of FSH and meiosis-activating sterol, indicating that induced maturation also uses the cAMP-protein kinase A-dependent signal transduction pathway. In conclusion, induced and spontaneous maturation of mouse oocytes appear to use different signal transduction pathways.


1994 ◽  
Vol 269 (5) ◽  
pp. 3534-3538
Author(s):  
P.L. Hordijk ◽  
I. Verlaan ◽  
K. Jalink ◽  
E.J. van Corven ◽  
W.H. Moolenaar

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