schliessen

Filtern

 

Bibliotheken

Plasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins.

Plasma membrane (PM) localization of Ras proteins is crucial for transmitting signals upon mitogen stimulation. Posttranslational lipid modification of Ras proteins plays an important role in their recruitment to the PM. Electrostatic interactions between negatively charged PM phospholipids and basi... Full description

Journal Title: The Journal of biological chemistry November 17, 2017, Vol.292(46), pp.18862-18877
Main Author: Gulyás, Gergő
Other Authors: Radvánszki, Glória , Matuska, Rita , Balla, András , Hunyady, László , Balla, Tamas , Várnai, Péter
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1083-351X ; DOI: 10.1074/jbc.M117.806679
Link: http://search.proquest.com/docview/1942706079/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1942706079
title: Plasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins.
format: Article
creator:
  • Gulyás, Gergő
  • Radvánszki, Glória
  • Matuska, Rita
  • Balla, András
  • Hunyady, László
  • Balla, Tamas
  • Várnai, Péter
subjects:
  • Animals–Metabolism
  • Cos Cells–Metabolism
  • Cell Membrane–Metabolism
  • Cercopithecus Aethiops–Metabolism
  • Diphosphates–Metabolism
  • Golgi Apparatus–Metabolism
  • Hek293 Cells–Metabolism
  • Humans–Metabolism
  • Phosphatidylinositol Phosphates–Metabolism
  • Protein Transport–Metabolism
  • Proto-Oncogene Proteins P21(Ras)–Metabolism
  • Diphosphates
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositol 4-Phosphate
  • K-Ras4b Protein, Human
  • Hras Protein, Human
  • Proto-Oncogene Proteins P21(Ras)
  • G Protein-Coupled Receptor (Gpcr)
  • Gtpase Kras (Kras)
  • Golgi
  • Bioluminescence Resonance Energy Transfer (Bret)
  • Phosphoinositide
ispartof: The Journal of biological chemistry, November 17, 2017, Vol.292(46), pp.18862-18877
description: Plasma membrane (PM) localization of Ras proteins is crucial for transmitting signals upon mitogen stimulation. Posttranslational lipid modification of Ras proteins plays an important role in their recruitment to the PM. Electrostatic interactions between negatively charged PM phospholipids and basic amino acids found in K-Ras4B (K-Ras) but not in H-Ras are important for permanent K-Ras localization to the PM. Here, we investigated how acute depletion of negatively charged PM polyphosphoinositides (PPIns) from the PM alters the intracellular distribution and activity of K- and H-Ras proteins. PPIns depletion from the PM was achieved either by agonist-induced activation of phospholipase C β or with a rapamycin-inducible system in which various PI phosphatases were recruited to the PM. Redistribution of the two Ras proteins was monitored with confocal microscopy or with a recently developed bioluminescent energy transfer (BRET)-based approach involving fusion of the Ras C-terminal targeting sequences or the entire Ras proteins to Venus fluorescent protein. We found that PM PPIns depletion caused rapid translocation of K-Ras but not H-Ras from the PM to the Golgi. PM depletion of either phosphatidylinositol 4-phosphate (PtdIns4P) or PtdIns(4,5)P2, but not PtdIns(3,4,5)P3, was sufficient to evoke K-Ras translocation. This effect was diminished by deltarasine, an inhibitor of the Ras-phosphodiesterase interaction, or by simultaneous depletion of the Golgi PtdIns4P. The PPIns depletion decreased incorporation of [3H]-Leucine in K-Ras-expressing cells, suggesting that Golgi-localized K-Ras is not as signaling competent as its PM-bound form. We conclude that PPIns in the PM are important regulators of K-Ras mediated signals.
language: eng
source:
identifier: E-ISSN: 1083-351X ; DOI: 10.1074/jbc.M117.806679
fulltext: fulltext
issn:
  • 1083351X
  • 1083-351X
url: Link


@attributes
ID1488974159
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1942706079
sourceidproquest
recordidTN_proquest1942706079
sourcesystemPC
pqid1942706079
display
typearticle
titlePlasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins.
creatorGulyás, Gergő ; Radvánszki, Glória ; Matuska, Rita ; Balla, András ; Hunyady, László ; Balla, Tamas ; Várnai, Péter
contributorGulyás, Gergő (correspondence author) ; Gulyás, Gergő (record owner)
ispartofThe Journal of biological chemistry, November 17, 2017, Vol.292(46), pp.18862-18877
identifierE-ISSN: 1083-351X ; DOI: 10.1074/jbc.M117.806679
subjectAnimals–Metabolism ; Cos Cells–Metabolism ; Cell Membrane–Metabolism ; Cercopithecus Aethiops–Metabolism ; Diphosphates–Metabolism ; Golgi Apparatus–Metabolism ; Hek293 Cells–Metabolism ; Humans–Metabolism ; Phosphatidylinositol Phosphates–Metabolism ; Protein Transport–Metabolism ; Proto-Oncogene Proteins P21(Ras)–Metabolism ; Diphosphates ; Phosphatidylinositol Phosphates ; Phosphatidylinositol 4-Phosphate ; K-Ras4b Protein, Human ; Hras Protein, Human ; Proto-Oncogene Proteins P21(Ras) ; G Protein-Coupled Receptor (Gpcr) ; Gtpase Kras (Kras) ; Golgi ; Bioluminescence Resonance Energy Transfer (Bret) ; Phosphoinositide
languageeng
source
descriptionPlasma membrane (PM) localization of Ras proteins is crucial for transmitting signals upon mitogen stimulation. Posttranslational lipid modification of Ras proteins plays an important role in their recruitment to the PM. Electrostatic interactions between negatively charged PM phospholipids and basic amino acids found in K-Ras4B (K-Ras) but not in H-Ras are important for permanent K-Ras localization to the PM. Here, we investigated how acute depletion of negatively charged PM polyphosphoinositides (PPIns) from the PM alters the intracellular distribution and activity of K- and H-Ras proteins. PPIns depletion from the PM was achieved either by agonist-induced activation of phospholipase C β or with a rapamycin-inducible system in which various PI phosphatases were recruited to the PM. Redistribution of the two Ras proteins was monitored with confocal microscopy or with a recently developed bioluminescent energy transfer (BRET)-based approach involving fusion of the Ras C-terminal targeting sequences or the entire Ras proteins to Venus fluorescent protein. We found that PM PPIns depletion caused rapid translocation of K-Ras but not H-Ras from the PM to the Golgi. PM depletion of either phosphatidylinositol 4-phosphate (PtdIns4P) or PtdIns(4,5)P2, but not PtdIns(3,4,5)P3, was sufficient to evoke K-Ras translocation. This effect was diminished by deltarasine, an inhibitor of the Ras-phosphodiesterase interaction, or by simultaneous depletion of the Golgi PtdIns4P. The PPIns depletion decreased incorporation of [3H]-Leucine in K-Ras-expressing cells, suggesting that Golgi-localized K-Ras is not as signaling competent as its PM-bound form. We conclude that PPIns in the PM are important regulators of K-Ras mediated signals.
version3
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1942706079/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Gulyás, Gergő
1Radvánszki, Glória
2Matuska, Rita
3Balla, András
4Hunyady, László
5Balla, Tamas
6Várnai, Péter
titlePlasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins.
subject
0Animals–Metabolism
1Cos Cells–Metabolism
2Cell Membrane–Metabolism
3Cercopithecus Aethiops–Metabolism
4Diphosphates–Metabolism
5Golgi Apparatus–Metabolism
6Hek293 Cells–Metabolism
7Humans–Metabolism
8Phosphatidylinositol Phosphates–Metabolism
9Protein Transport–Metabolism
10Proto-Oncogene Proteins...
11G protein-coupled receptor (GPCR)
12GTPase Kras (KRAS)
13Golgi
14bioluminescence resonance energy transfer (BRET)
15phosphoinositide
general
0English
110.1074/jbc.M117.806679
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1942706079
issn
01083351X
11083-351X
rsrctypearticle
creationdate2017
addtitleThe Journal of biological chemistry
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributorGulyás, Gergő
startdate20171117
enddate20171117
citationpf 18862 pt 18877 vol 292 issue 46
lsr30VSR-Enriched:[issn, pqid, description]
sort
titlePlasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins.
authorGulyás, Gergő ; Radvánszki, Glória ; Matuska, Rita ; Balla, András ; Hunyady, László ; Balla, Tamas ; Várnai, Péter
creationdate20171117
lso0120171117
facets
frbrgroupid8423456190292723309
frbrtype5
newrecords20181218
languageeng
creationdate2017
topic
0Animals–Metabolism
1Cos Cells–Metabolism
2Cell Membrane–Metabolism
3Cercopithecus Aethiops–Metabolism
4Diphosphates–Metabolism
5Golgi Apparatus–Metabolism
6Hek293 Cells–Metabolism
7Humans–Metabolism
8Phosphatidylinositol Phosphates–Metabolism
9Protein Transport–Metabolism
10Proto-Oncogene Proteins...
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Gulyás, Gergő
1Radvánszki, Glória
2Matuska, Rita
3Balla, András
4Hunyady, László
5Balla, Tamas
6Várnai, Péter
jtitleJournal of biological chemistry
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Gulyás
1Radvánszki
2Matuska
3Balla
4Hunyady
5Várnai
aufirst
0Gergő
1Glória
2Rita
3András
4László
5Tamas
6Péter
au
0Gulyás, Gergő
1Radvánszki, Glória
2Matuska, Rita
3Balla, András
4Hunyady, László
5Balla, Tamas
6Várnai, Péter
addauGulyás, Gergő
atitlePlasma membrane phosphatidylinositol 4-phosphate and 4,5-bisphosphate determine the distribution and function of K-Ras4B but not H-Ras proteins.
jtitleThe Journal of biological chemistry
risdate20171117
volume292
issue46
spage18862
epage18877
pages18862-18877
eissn1083-351X
formatjournal
genrearticle
ristypeJOUR
doi10.1074/jbc.M117.806679
urlhttp://search.proquest.com/docview/1942706079/
issn00219258
date2017-11-17