Mitogenesis in Response to PDGF and Bombesin Abolished by Microinjection of Antibody to PIP
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Matuoka, Koozi; Fukami, Kiyoko; Nakanishi, Osamu; Kawai, Sadaaki; Takenawa, Tadaomi

doi:10.1126/science.2829356

Cited by 145 publications

(69 citation statements)

References 34 publications

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“…This characteristic of ARDs is comparable to that of antibodies, in that antibodies can be generated against lipids, including PI(4,5)P 2 (ref. 52). Therefore, the highly diverse characteristics of ARDs may support their ability to recognize a variety of molecules, including lipids.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

et al. 2014

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Mutations in the ankyrin repeat domain (ARD) of TRPV4 are responsible for several channelopathies, including Charcot-Marie-Tooth disease type 2C and congenital distal and scapuloperoneal spinal muscular atrophy. However, the molecular pathogenesis mediated by these mutations remains elusive, mainly due to limited understanding of the TRPV4 ARD function. Here we show that phosphoinositide binding to the TRPV4 ARD leads to suppression of the channel activity. Among the phosphoinositides, phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ) most potently binds to the TRPV4 ARD. The crystal structure of the TRPV4 ARD in complex with inositol-1,4,5-trisphosphate, the head-group of PI(4,5)P 2 , and the molecular-dynamics simulations revealed the PI(4,5)P 2 -binding amino-acid residues. The TRPV4 channel activities were increased by titration or hydrolysis of membrane PI(4,5)P 2 . Notably, disease-associated TRPV4 mutations that cause a gain-of-function phenotype abolished PI(4,5)P 2 binding and PI(4,5)P 2 sensitivity. These findings identify TRPV4 ARD as a lipid-binding domain in which interactions with PI(4,5)P 2 normalize the channel activity in TRPV4.

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Section: Discussionmentioning

confidence: 99%

TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

et al. 2014

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“…and immunostained with antion. Monoclonal antibody to PtdIns(4,5)P2 was prepared as described before [24,25].…”

Section: Preparation Of Antibodies Polyclonal Antibodies To His-mentioning

confidence: 99%

“…[ 3 H]PtdIns(4,5)P 2 (7.6 Ci/mmol) and proteins using a monoclonal antibody to PtdIns(4,5)P 2 , which is [γ-32 P]ATP were purchased from Du Pont New England Nuclear very specific and does not recognize other phospholipids such and Amersham, respectively. Drosophila embryo nuclear extract as PtdIns and PtdIns4P [24,25]. Using this antibody, we have in vitro transcription system was from Promega.…”

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confidence: 99%

Phosphatidylinositol 4,5‐bisphosphate reverses the inhibition of RNA transcription caused by histone H1

Fukami

Watanabe

et al. 1998

European Journal of Biochemistry

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108

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Phosphatidylinositol 4,5-bisphosphate [PtdIns(4, 5)P 2 ] has been known to bind to the pleckstrin homology domain and the phosphotyrosine-binding domain as well as actin-binding proteins, and to regulate their functions. We have tried to find new PtdIns(4,5)P 2 -binding proteins and to clarify the physiological effects of PtdIns(4,5)P 2 on their function. We report here that histones H1 and H3 are PtdIns(4,5)P 2 -binding proteins which were identified using antibodies specific to PtdIns(4,5)P 2 , H1, and H3. This binding was further confirmed by extracting PtdIns(4,5)P 2 from purified histone H1 and H3. Furthermore, the binding site of PtdIns(4,5)P 2 in histone H1 was found in the carboxyl-terminal 103 amino acids. It was also shown that the amounts of PtdIns(4,5)P 2 bound to H1 decrease when histone H1 is phosphorylated by protein kinase C but not by protein kinase A or cdc2 kinase, in vitro. The protein kinase C phosphorylation site is localized close to the PtdIns(4,5)P 2-binding site, suggesting that phosphorylation of histone H1 by protein kinase C interferes stereostructually with PtdIns(4,5)P 2 binding. We further noticed that PtdIns(4,5)P 2 binding to H1 counteracts the histone H1-mediated repression of basal transcription by RNA polymerase II in a Drosophila transcription system in vitro. Phosphatidylinositol 4-phosphate and phosphatidylinositol 3,4,5-trisphosphate affect this transcription activity more weakly than PtdIns(4,5)P 2 , but PtdIns and other acidic lipids have no effect on this activity. These data indicate that PtdIns(4,5)P 2 bound to nuclear protein histone H1 may contribute to the regulation of transcription in eukaryotic cells.Keywords : phosphatidylinositol 4,5-bisphosphate; histone H1; phosphorylation; transcription; nucleus.Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ] is rec-ates second messengers, but also modulates the function of ognized as the source of the bioactive second messenger inositol PtdIns(4,5)P 2 -binding proteins. trisphosphate [Ins(1, 4, 5)P 3 ] for intracellular Ca 2ϩ mobilization Increasing evidence indicates that PtdIns(4,5)P 2 is present and diacylglycerol for protein kinase C (PKC) activation. In in the nuclear membrane and nuclear matrix as well as in addition to its role as a signal-generating lipid, PtdIns(4,5)P 2 has the plasma membrane and cytoplasmic cytoskeleton. Likewise, been shown to modulate the functions of various proteins such the isolated membrane-free nuclei from Friend erythroleukemia as PKC [1,2], µ-calpain [3], ADP-ribosylation factor 1 [4], and cells have enzymes that produce both PtdIns4P and phospholipase D [5]. PtdIns(4,5)P 2 also binds to actin-regulating PtdIns(4,5)P 2 [14], and a decrease in nuclear PtdIns4P and proteins such as profilin [6], cofilin [7], gelsolin [8], gCap [9], PtdIns(4,5)P 2 was observed in Swiss 3T3 cells in the early stages and A-actinin [10] and regulates the functions of these pro-of the response to insulin like growth factor 1 [15] and in HeLa teins. It has been reported that a decrease in the amount of...

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“…Available data have largely suggested that PDGF receptor mediates inositol phosphate generation through mechanisms independent of toxinsensitive G proteins (23)(24)(25)(26)(27)(28)(29). At least five distinct proteins with PLC activity have been identified and cloned, differing in tissue distribution, substrate specificity, and Ca2+ and pH dependence (30).…”

mentioning

confidence: 99%

Platelet-derived growth factor (PDGF) binding promotes physical association of PDGF receptor with phospholipase C.

Kumjian

Wahl

Rhee

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

200

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Phospholipase C (PLC)-mediated production of inositol trisphosphate and diacylglycerol is stimulated by binding of platelet-derived growth factor (PDGF) to cell-surface receptors. Antibodies recognizing native PDGF receptors through peptide-domain epitopes coprecipitated 4-fold more PLC activity with receptors from PDGF-stimulated than from unstimulated BALB/c 3T3 cells, despite equivalent PDGF receptor recovery. Activity coprecipitated from unstimulated cells was comparable to nonspecific activity recovered with preimmune sera or in the presence of competing peptide immunogen. PLC activity coprecipitating with PDGF receptors represented 60% of anti-phosphotyrosine antibody-recovered activity from PDGF-stimulated cells. Coprecipitation was rapidly induced in cells treated with PDGF at 4 degrees C, reversibly lost with acid dissociation of PDGF from receptors, and recovered with PDGF readdition. PDGF concentrations effecting coprecipitation correlated with stimulation of intact-cell inositol phosphate production. Monoclonal antibodies to PLC gamma (145 kDa) coprecipitated from PDGF-stimulated cell lysates (but not from unstimulated cell lysates) tyrosine kinase activity that phosphorylated PDGF receptor and PLC gamma. Stable physical association of PDGF receptors with PLC may participate in coupling ligand binding to increased PLC activity.

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Mitogenesis in Response to PDGF and Bombesin Abolished by Microinjection of Antibody to PIP ₂

Cited by 145 publications

References 34 publications

TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

Phosphatidylinositol 4,5‐bisphosphate reverses the inhibition of RNA transcription caused by histone H1

Platelet-derived growth factor (PDGF) binding promotes physical association of PDGF receptor with phospholipase C.

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Mitogenesis in Response to PDGF and Bombesin Abolished by Microinjection of Antibody to PIP 2

Cited by 145 publications

References 34 publications

TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

Phosphatidylinositol 4,5‐bisphosphate reverses the inhibition of RNA transcription caused by histone H1

Platelet-derived growth factor (PDGF) binding promotes physical association of PDGF receptor with phospholipase C.

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Mitogenesis in Response to PDGF and Bombesin Abolished by Microinjection of Antibody to PIP ₂