An essential role for phosphatidylinositol transfer protein in phospholipase C-Mediated inositol lipid signaling
Abstract
Transmembrane signaling by the phospholipase C-beta (PLC-beta) pathway is known to require at least three components: the receptor, the G protein, and the PLC. Recent studies have indicated that if the cytosol is allowed to leak out of HL60 cells, then G protein-stimulated PLC activity is greatly diminished, indicating an essential role for a cytosolic component(s). We now report the complete purification of one component based on its ability to reconstitute GTP gamma S-mediated PLC activity and identify it as the phosphatidylinositol transfer protein (PI-TP). Based on the in vitro effects of PI-TP, we surmise that it is involved in transporting PI from intracellular compartments for conversion to PI bisphosphate (PIP2) prior to hydrolysis by PLC-beta 2/PLC-beta 3, the endogenous PLC isoforms present in these cells.
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Lipid transfer of PI and PA between plasma membrane and ER is accomplished by PITPs.
“Due to the topological arrangement of the enzymes present in separate membrane compartments (i.e. plasma membrane and ER), lipid transfer of PI and PA has to take place. This is accomplished by a family of PI transfer proteins (PITPs) [23–26].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [25]
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Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176 · see citing works
Self-citation
- Authors
- Thomas, G. M. H., Cunningham, E., Fensome, A., Ball, A., Totty, N. F., Truong, O., Hsuan, J. J., & Cockcroft, S.
- Affiliations
- University College London (GB)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1993-09
- Volume
- 74
- Issue
- 5
- Pages
- 919-928
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1970666556
- Cited by
- 207
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 1 · 2013: 3 · 2012: 3
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- phosphatidylinositol transfer protein, phospholipase C beta, inositol lipid signaling, phosphatidylinositol bisphosphate, G protein signaling, HL-60 cells
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cell Membrane, Humans, Kinetics, Membrane Proteins, Molecular Sequence Data, Phosphatidylinositols, Type C Phospholipases, Tumor Cells, Cultured, Immunoblotting, Signal Transduction, Leukemia, Promyelocytic, Acute, Guanosine 5'-O-(3-Thiotriphosphate), Sequence Homology, Amino Acid, GTP-Binding Proteins, Saccharomyces cerevisiae Proteins, Phospholipid Transfer Proteins, Rats
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