Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase biology
Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, cent...
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| Published in | Biochimica et biophysica acta Vol. 1851; no. 6; pp. 724 - 735 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.06.2015
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in this regard that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. This article is part of a Special Issue entitled Phosphoinositides.
•Historical views of PITPs as lipid transfer proteins are reassessed.•PITPs channel lipid kinase activities to specific biological outcomes.•Mechanisms of functional channeling rest on PITP ligand specificities.•PITP lipid exchange cycle is an engine for potentiating lipid kinase catalytic efficiency. |
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| AbstractList | Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in these regards that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in this regard that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. This article is part of a Special Issue entitled Phosphoinositides. Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in this regard that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. This article is part of a Special Issue entitled Phosphoinositides.Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in this regard that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. This article is part of a Special Issue entitled Phosphoinositides. Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in this regard that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. This article is part of a Special Issue entitled Phosphoinositides. •Historical views of PITPs as lipid transfer proteins are reassessed.•PITPs channel lipid kinase activities to specific biological outcomes.•Mechanisms of functional channeling rest on PITP ligand specificities.•PITP lipid exchange cycle is an engine for potentiating lipid kinase catalytic efficiency. |
| Author | Khan, Danish Bankaitis, Vytas A. Grabon, Aby |
| AuthorAffiliation | 1 Department of Molecular & Cellular Medicine Texas A&M Health Science Center College Station, TX 77843-1114 U.S.A 2 Department of Biochemistry & Biophysics Texas A&M University College Station, TX 77843-2128 U.S.A |
| AuthorAffiliation_xml | – name: 1 Department of Molecular & Cellular Medicine Texas A&M Health Science Center College Station, TX 77843-1114 U.S.A – name: 2 Department of Biochemistry & Biophysics Texas A&M University College Station, TX 77843-2128 U.S.A |
| Author_xml | – sequence: 1 givenname: Aby surname: Grabon fullname: Grabon, Aby organization: Department of Molecular & Cellular Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA – sequence: 2 givenname: Danish orcidid: 0000-0002-0650-3990 surname: Khan fullname: Khan, Danish organization: Department of Biochemistry & Biophysics, Texas A&M University, College Station, TX 77843-2128, USA – sequence: 3 givenname: Vytas A. surname: Bankaitis fullname: Bankaitis, Vytas A. email: vytas@tamhsc.edu organization: Department of Molecular & Cellular Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25592381$$D View this record in MEDLINE/PubMed |
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| Copyright | 2015 Elsevier B.V. Copyright © 2015 Elsevier B.V. All rights reserved. |
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| Keywords | Signaling diversity Phosphatidylinositol transfer proteins Regulation of lipid kinases |
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| SubjectTerms | Biological Transport CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase - genetics CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase - metabolism enzymes eukaryotic cells Gene Expression Regulation Humans inositol phosphates Lipid Metabolism lipids Models, Molecular Phosphatidylinositol transfer proteins Phosphatidylinositols - metabolism Phospholipid Transfer Proteins - genetics Phospholipid Transfer Proteins - metabolism Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - metabolism physiology proteins Regulation of lipid kinases Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Signal Transduction Signaling diversity Type C Phospholipases - genetics Type C Phospholipases - metabolism |
| Title | Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase biology |
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