Lysophosphatidic acid activates the 70-kDa S6 kinase via the lipoxygenase pathway.
Many hormones are known to activate the 70-kDa S6 kinase (p70(S6K)). The signalling pathways mediating p70(S6K) activation are only partially characterized. We investigate, in this report, the mechanisms by which lysophosphatidic acid (LPA) activates p70(S6K). We observed that p70(S6K) activation was conventional, in that it was sensitive to both rapamycin and PI3 kinase inhibition. p70(S6K) 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 p70(S6K) activation. Similarly, the effect of LPA on p70(S6K) 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 A(2) and lipoxygenase pathways attenuated p70(S6K) activation indicating a novel mechanism of p70(S6K) regulation. We conclude that in Swiss 3T3 cells LPA coordinates activation of several phospholipases to regulate p70(S6K).
Willard
F S
FS
Molecular Signalling Group, Australian National University, Canberra, ACT 2601, Australia. francis.willard@anu.edu.au
Berven
L A
LA
Crouch
M F
MF
D016475:3T3 Cells; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation; D008084:Lipoxygenase / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D008246:Lysophospholipids; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016718:Arachidonic Acid; D008084:Lipoxygenase; D019893:Ribosomal Protein S6 Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D010738:Type C Phospholipases; D010739:Phospholipase D; D002118:Calcium; D020123:Sirolimus