5jhb - Revision history

OCA at 18:52, 20 September 2023

OCA — Wed, 20 Sep 2023 18:52:06 GMT

←Older revision		Revision as of 18:52, 20 September 2023
Line 3:		Line 3:
	<StructureSection load='5jhb' size='340' side='right'caption='[[5jhb]], [[Resolution\|resolution]] 2.48Å' scene=''>		<StructureSection load='5jhb' size='340' side='right'caption='[[5jhb]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5jhb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JHB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5JHB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5jhb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JHB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JHB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6K5:[1-{4-[6-AMINO-4-(TRIFLUOROMETHYL)PYRIDIN-3-YL]-6-(MORPHOLIN-4-YL)-1,3,5-TRIAZIN-2-YL}-3-(CHLOROMETHYL)AZETIDIN-3-YL]METHANOL'>6K5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.48Å</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5jhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jhb OCA], [~~http~~://pdbe.org/5jhb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5jhb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5jhb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5jhb ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6K5:[1-{4-[6-AMINO-4-(TRIFLUOROMETHYL)PYRIDIN-3-YL]-6-(MORPHOLIN-4-YL)-1,3,5-TRIAZIN-2-YL}-3-(CHLOROMETHYL)AZETIDIN-3-YL]METHANOL'>6K5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5jhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jhb OCA], [https://pdbe.org/5jhb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jhb RCSB], [https://www.ebi.ac.uk/pdbsum/5jhb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jhb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>	+	[https://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Burke~~, J E~~]]	+	[[Category: Burke JE]]
-	[[Category: Inglis~~, A J~~]]	+	[[Category: Inglis AJ]]
-	[[Category: Williams~~, R L]]~~	+	[[Category: Williams RL]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Lipid kinase]]~~	+
-	~~[[Category: Pi3k]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 07:48, 10 June 2020

OCA — Wed, 10 Jun 2020 07:48:53 GMT

←Older revision		Revision as of 07:48, 10 June 2020
Line 1:		Line 1:

	==Structure of Phosphoinositide 3-kinase gamma (PI3K) bound to the potent inhibitor PIKin3==		==Structure of Phosphoinositide 3-kinase gamma (PI3K) bound to the potent inhibitor PIKin3==
-	<StructureSection load='5jhb' size='340' side='right' caption='[[5jhb]], [[Resolution\|resolution]] 2.48Å' scene=''>	+	<StructureSection load='5jhb' size='340' side='right'caption='[[5jhb]], [[Resolution\|resolution]] 2.48Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5jhb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JHB OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5JHB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5jhb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JHB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JHB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6K5:[1-{4-[6-AMINO-4-(TRIFLUOROMETHYL)PYRIDIN-3-YL]-6-(MORPHOLIN-4-YL)-1,3,5-TRIAZIN-2-YL}-3-(CHLOROMETHYL)AZETIDIN-3-YL]METHANOL'>6K5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6K5:[1-{4-[6-AMINO-4-(TRIFLUOROMETHYL)PYRIDIN-3-YL]-6-(MORPHOLIN-4-YL)-1,3,5-TRIAZIN-2-YL}-3-(CHLOROMETHYL)AZETIDIN-3-YL]METHANOL'>6K5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5jhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jhb OCA], [http://pdbe.org/5jhb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jhb RCSB], [http://www.ebi.ac.uk/pdbsum/5jhb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jhb ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jhb OCA], [http://pdbe.org/5jhb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jhb RCSB], [http://www.ebi.ac.uk/pdbsum/5jhb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jhb ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 20:

	==See Also==		==See Also==
-	*[[Phosphoinositide 3-~~Kinases~~\|Phosphoinositide 3-~~Kinases~~]]	+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Burke, J E]]		[[Category: Burke, J E]]
	[[Category: Inglis, A J]]		[[Category: Inglis, A J]]

OCA at 07:23, 6 October 2017

OCA — Fri, 06 Oct 2017 07:23:46 GMT

←Older revision		Revision as of 07:23, 6 October 2017
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5jhb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5jhb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:43, 22 March 2017

OCA — Wed, 22 Mar 2017 09:43:03 GMT

←Older revision		Revision as of 09:43, 22 March 2017
Line 9:		Line 9:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>		[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BKM120 (Buparlisib) is one of the most advanced phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of cancer, but it interferes as an off-target effect with microtubule polymerization. Here, we developed two chemical derivatives that differ from BKM120 by only one atom. We show that these minute changes separate the dual activity of BKM120 into discrete PI3K and tubulin inhibitors. Analysis of the compounds cellular growth arrest phenotypes and microtubule dynamics suggest that the antiproliferative activity of BKM120 is mainly due to microtubule-dependent cytotoxicity rather than through inhibition of PI3K. Crystal structures of BKM120 and derivatives in complex with tubulin and PI3K provide insights into the selective mode of action of this class of drugs. Our results raise concerns over BKM120's generally accepted mode of action, and provide a unique mechanistic basis for next-generation PI3K inhibitors with improved safety profiles and flexibility for use in combination therapies.
		+
		+	Deconvolution of Buparlisib's mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention.,Bohnacker T, Prota AE, Beaufils F, Burke JE, Melone A, Inglis AJ, Rageot D, Sele AM, Cmiljanovic V, Cmiljanovic N, Bargsten K, Aher A, Akhmanova A, Diaz JF, Fabbro D, Zvelebil M, Williams RL, Steinmetz MO, Wymann MP Nat Commun. 2017 Mar 9;8:14683. doi: 10.1038/ncomms14683. PMID:28276440<ref>PMID:28276440</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5jhb" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:19, 15 March 2017

OCA — Wed, 15 Mar 2017 21:19:50 GMT

←Older revision		Revision as of 21:19, 15 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5jhb is ~~ON HOLD~~	+	==Structure of Phosphoinositide 3-kinase gamma (PI3K) bound to the potent inhibitor PIKin3==
-		+	<StructureSection load='5jhb' size='340' side='right' caption='[[5jhb]], [[Resolution\|resolution]] 2.48Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5jhb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JHB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JHB FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6K5:[1-{4-[6-AMINO-4-(TRIFLUOROMETHYL)PYRIDIN-3-YL]-6-(MORPHOLIN-4-YL)-1,3,5-TRIAZIN-2-YL}-3-(CHLOROMETHYL)AZETIDIN-3-YL]METHANOL'>6K5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jhb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jhb OCA], [http://pdbe.org/5jhb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jhb RCSB], [http://www.ebi.ac.uk/pdbsum/5jhb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jhb ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PK3CG_HUMAN PK3CG_HUMAN]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to ADRBK1 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.<ref>PMID:7624799</ref> <ref>PMID:12163475</ref> <ref>PMID:15294162</ref> <ref>PMID:16094730</ref> <ref>PMID:21393242</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Burke, J E]]
		+	[[Category: Inglis, A J]]
		+	[[Category: Williams, R L]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lipid kinase]]
		+	[[Category: Pi3k]]
		+	[[Category: Transferase]]

OCA at 15:25, 15 May 2016

OCA — Sun, 15 May 2016 15:25:16 GMT

←Older revision		Revision as of 15:25, 15 May 2016
Line 3:		Line 3:
	The entry 5jhb is ON HOLD		The entry 5jhb is ON HOLD

-	Authors: ~~Burke, J.E., Inglis, A.J., Williams, R.L.~~	+	Authors:

	Description:		Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Inglis, A.J]]
-	[[Category: Burke, J.E]]
-	[[Category: Williams, R.L]]

OCA: Protected "5jhb" [edit=sysop:move=sysop]

OCA — Wed, 11 May 2016 02:04:16 GMT

Protected "5jhb" [edit=sysop:move=sysop]

←Older revision

Revision as of 02:04, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5jhb is ON HOLD Authors: Burke, J.E., Inglis, A.J., Williams, R.L. Description: Category: Unreleased Structures Category: Inglis, A.J [[Ca...

OCA — Wed, 11 May 2016 02:04:15 GMT

New page: '''Unreleased structure''' The entry 5jhb is ON HOLD Authors: Burke, J.E., Inglis, A.J., Williams, R.L. Description: Category: Unreleased Structures Category: Inglis, A.J [[Ca...

New page

'''Unreleased structure'''

The entry 5jhb is ON HOLD

Authors: Burke, J.E., Inglis, A.J., Williams, R.L.

Description:
[[Category: Unreleased Structures]]
[[Category: Inglis, A.J]]
[[Category: Burke, J.E]]
[[Category: Williams, R.L]]