Lysophosphatidic Acid Activates the 70-kDa S6 Kinase via the Lipoxygenase Pathway

Many hormones are known to activate the 70-kDa S6 kinase (p70S6K). The signalling pathways mediating p70S6K activation are only partially characterized. We investigate, in this report, the mechanisms by which lysophosphatidic acid (LPA) activates p70S6K. We observed that p70S6K activation was conven...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-09, Vol.287 (3), p.607-613
Main Authors: Willard, Francis S., Berven, Leise A., Crouch, Michael F.
Format: Article
Language:English
Subjects:
3T3 Cells
70-kDa S6 kinase
Animals
arachidonic acid
Arachidonic Acid - metabolism
Calcium - metabolism
Calcium - pharmacology
Enzyme Activation
lipoxygenase
Lipoxygenase - metabolism
lysophosphatidic acid
Lysophospholipids - metabolism
Mice
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
phospholipase A2
phospholipase C
phospholipase D
Phospholipase D - metabolism
Phospholipases A - antagonists & inhibitors
Phospholipases A - metabolism
protein kinase C
Protein Kinase C - metabolism
Ribosomal Protein S6 Kinases - metabolism
Signal Transduction
Sirolimus - pharmacology
Type C Phospholipases - metabolism
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Summary:Many hormones are known to activate the 70-kDa S6 kinase (p70S6K). The signalling pathways mediating p70S6K activation are only partially characterized. We investigate, in this report, the mechanisms by which lysophosphatidic acid (LPA) activates p70S6K. We observed that p70S6K activation was conventional, in that it was sensitive to both rapamycin and PI3 kinase inhibition. p70S6K activation appeared to be caused by the activation of several phospholipase pathways. LPA was an effective stimulus of phospholipase C induced intracellular calcium mobilization, which appeared to participate in p70S6K activation. Similarly, the effect of LPA on p70S6K activity was antagonized by butan-1-ol but not butan-2-ol suggesting the involvement of agonist stimulated phospholipase D activity. Further, antagonism of the phospholipase A2 and lipoxygenase pathways attenuated p70S6K activation indicating a novel mechanism of p70S6K regulation. We conclude that in Swiss 3T3 cells LPA coordinates activation of several phospholipases to regulate p70S6K.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5645