Lysophosphatidic acid activates the 70-kDa S6 kinase via the lipoxygenase pathway

Francis S. Willard; Leise A. Berven; Michael F. Crouch

doi:10.1006/bbrc.2001.5645

Lysophosphatidic acid activates the 70-kDa S6 kinase via the lipoxygenase pathway

Francis S. Willard^*, Leise A. Berven, Michael F. Crouch

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

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 A₂ 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.

Original language	English
Pages (from-to)	607-613
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	287
Issue number	3
DOIs	https://doi.org/10.1006/bbrc.2001.5645
Publication status	Published - 28 Sept 2001

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@article{4e15e4757aac4b65af925dd1603985c4,

title = "Lysophosphatidic acid activates the 70-kDa S6 kinase via the lipoxygenase pathway",

abstract = "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.",

keywords = "70-kDa S6 kinase, Arachidonic acid, Lipoxygenase, Lysophosphatidic acid, Phospholipase A, Phospholipase C, Phospholipase D, Protein kinase C",

author = "Willard, {Francis S.} and Berven, {Leise A.} and Crouch, {Michael F.}",

year = "2001",

month = sep,

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doi = "10.1006/bbrc.2001.5645",

language = "English",

volume = "287",

pages = "607--613",

journal = "Biochemical and Biophysical Research Communications",

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T1 - Lysophosphatidic acid activates the 70-kDa S6 kinase via the lipoxygenase pathway

AU - Willard, Francis S.

AU - Berven, Leise A.

AU - Crouch, Michael F.

PY - 2001/9/28

Y1 - 2001/9/28

N2 - 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.

AB - 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.

KW - 70-kDa S6 kinase

KW - Arachidonic acid

KW - Lipoxygenase

KW - Lysophosphatidic acid

KW - Phospholipase A

KW - Phospholipase C

KW - Phospholipase D

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=0035964877&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2001.5645

DO - 10.1006/bbrc.2001.5645

M3 - Article

SN - 0006-291X

VL - 287

SP - 607

EP - 613

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Lysophosphatidic acid activates the 70-kDa S6 kinase via the lipoxygenase pathway

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