Involvement of phosphatidylinositol 3'-kinase in stem-cell-factor-induced phospholipase D activation and arachidonic acid release
Kozawa, Osamu ; Blume-Jensen, Peter ; Heldin, Carl-Henrik and Rönnstrand, Lars LU
(1997)
In European Journal of Biochemistry
248(1).
p.149-155
- Abstract
- We have shown previously that the stem cell factor (SCF) receptor undergoes phosphorylation on serine residues following ligand stimulation, and that this phopshorylation is dependent mainly on the activity of protein kinase C (PKC). In the present study, we have further investigated the molecular mechanisms behind SCF-stimulated activation of PKC, and found that SCF does not activate phosphatidylinositol-specific phospholipase C. In contrast, phospholipase D (PLD) is activated in response to SCF in a dose-dependent manner. Activation of PLD was not inhibited by calphostin C, an inhibitor of PKC. On the other hand, inhibitors of phosphatidylinositol PtdIns 3'-kinase (PtdIns 3'-kinase), i.e. wortmannin and LY294002, inhibited SCF-induced... (More)
- We have shown previously that the stem cell factor (SCF) receptor undergoes phosphorylation on serine residues following ligand stimulation, and that this phopshorylation is dependent mainly on the activity of protein kinase C (PKC). In the present study, we have further investigated the molecular mechanisms behind SCF-stimulated activation of PKC, and found that SCF does not activate phosphatidylinositol-specific phospholipase C. In contrast, phospholipase D (PLD) is activated in response to SCF in a dose-dependent manner. Activation of PLD was not inhibited by calphostin C, an inhibitor of PKC. On the other hand, inhibitors of phosphatidylinositol PtdIns 3'-kinase (PtdIns 3'-kinase), i.e. wortmannin and LY294002, inhibited SCF-induced PLD activation. Moreover, a mutant SCF receptor in which Tyr721, which is responsible for activation of PtdIns 3'-kinase, is mutated to a phenylalanine residue was unable to mediate activation of PLD. Thus, PtdIns 3'-kinase appears to be essential for SCF-induced PLD activation. Furthermore, we demonstrate that phosphatidic acid (PtdH), generated through the action of PLD in response to SCF, is metabolized to diacylglycerol by dephosphorylation. Diacylglycerol can then activate PKC, and, moreover, after deacylation by a diacylglycerol lipase, yield arachidonic acid, an important second messenger in cell signaling. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1783916
- author
- Kozawa, Osamu
; Blume-Jensen, Peter
; Heldin, Carl-Henrik
and Rönnstrand, Lars
LU
- publishing date
- 1997
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Complementary/geneticsDiglycerides/biosynthesisEnzyme Activation/drug effectsHumansModels, Arachidonic Acid/*metabolismBase SequenceCell LineDNA, BiologicalMutagenesis, Site-DirectedPhosphatidylinositol 3-KinasesPhosphatidylinositol Diacylglycerol-LyasePhosphoinositide Phospholipase CPhospholipase D/*metabolismPhosphotransferases (Alcohol Group Acceptor)/*metabolismPropranolol/pharmacologyProto-Oncogene Proteins c-kit/genetics/metabolismSecond Messenger SystemsStem Cell Factor/metabolism/*pharmacologyTransfectionType C Phospholipases/metabolism
- in
- European Journal of Biochemistry
- volume
- 248
- issue
- 1
- pages
- 149 - 155
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:0030835325
- ISSN
- 0014-2956
- DOI
- 10.1111/j.1432-1033.1997.00149.x
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- 06fc0d60-e8bb-4b48-afea-27c32c777809 (old id 1783916)
- alternative location
- http://onlinelibrary.wiley.com/doi/10.1111/j.1432-1033.1997.00149.x/full
- date added to LUP
- 2016-04-04 09:30:23
- date last changed
- 2022-01-29 18:10:59
@article{06fc0d60-e8bb-4b48-afea-27c32c777809,
abstract = {{We have shown previously that the stem cell factor (SCF) receptor undergoes phosphorylation on serine residues following ligand stimulation, and that this phopshorylation is dependent mainly on the activity of protein kinase C (PKC). In the present study, we have further investigated the molecular mechanisms behind SCF-stimulated activation of PKC, and found that SCF does not activate phosphatidylinositol-specific phospholipase C. In contrast, phospholipase D (PLD) is activated in response to SCF in a dose-dependent manner. Activation of PLD was not inhibited by calphostin C, an inhibitor of PKC. On the other hand, inhibitors of phosphatidylinositol PtdIns 3'-kinase (PtdIns 3'-kinase), i.e. wortmannin and LY294002, inhibited SCF-induced PLD activation. Moreover, a mutant SCF receptor in which Tyr721, which is responsible for activation of PtdIns 3'-kinase, is mutated to a phenylalanine residue was unable to mediate activation of PLD. Thus, PtdIns 3'-kinase appears to be essential for SCF-induced PLD activation. Furthermore, we demonstrate that phosphatidic acid (PtdH), generated through the action of PLD in response to SCF, is metabolized to diacylglycerol by dephosphorylation. Diacylglycerol can then activate PKC, and, moreover, after deacylation by a diacylglycerol lipase, yield arachidonic acid, an important second messenger in cell signaling.}},
author = {{Kozawa, Osamu and Blume-Jensen, Peter and Heldin, Carl-Henrik and Rönnstrand, Lars}},
issn = {{0014-2956}},
keywords = {{Complementary/geneticsDiglycerides/biosynthesisEnzyme Activation/drug effectsHumansModels; Arachidonic Acid/*metabolismBase SequenceCell LineDNA; BiologicalMutagenesis; Site-DirectedPhosphatidylinositol 3-KinasesPhosphatidylinositol Diacylglycerol-LyasePhosphoinositide Phospholipase CPhospholipase D/*metabolismPhosphotransferases (Alcohol Group Acceptor)/*metabolismPropranolol/pharmacologyProto-Oncogene Proteins c-kit/genetics/metabolismSecond Messenger SystemsStem Cell Factor/metabolism/*pharmacologyTransfectionType C Phospholipases/metabolism}},
language = {{eng}},
number = {{1}},
pages = {{149--155}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Biochemistry}},
title = {{Involvement of phosphatidylinositol 3'-kinase in stem-cell-factor-induced phospholipase D activation and arachidonic acid release}},
url = {{http://dx.doi.org/10.1111/j.1432-1033.1997.00149.x}},
doi = {{10.1111/j.1432-1033.1997.00149.x}},
volume = {{248}},
year = {{1997}},
}