Structural and Functional Roles of Glycosyl-Phosphatidylinositol in Membranes

Low, Martin G.; Saltiel, Alan R.

doi:10.1126/science.3276003

Cited by 947 publications

(442 citation statements)

References 150 publications

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“…It is known that a number of cell surface antigens, including Fhy-1, Qa-2, and TAP, are anchored to cell membranes with glycosylphosphatidylinositol (GPI) [1][2][3]. These GPI-anchored proteins have been shown to associate with non-receptor tyrosine kinases such as p56 l`h and p60/~" across the plasma membrane [4~6], and to transduce or modulate signals for promotion of protein tyrosine phosphorylation, increase the intracellular Ca 2+ level, and accelerate cell growth or cell death when crosslinked with specific antibodies [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Direct evidence of involvement of glycosylphosphatidylinositol‐anchored proteins in the heavy metal‐mediated signal delivery into T lymphocytes

Ohkusu

et al. 1995

FEBS Letters

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The biological significance of the action of glycosvlphosphatidylinositol (GPI)-anchored proteins in cell physiology and pathology when stimulated with their natural agonists is not known. Here we provide evidence that GPl-anchored proteins play a crucial role in the recently defined heavy metal (HgCI2)-triggered signal delivery to T lymphocytes. Thiol-reactive HgCI2, a multi-potent crosslinker of cell membrane proteins, induced heavy aggregation of Thy-l, a representative GPI-anchored prot ein, on murine thymocytes, and delivered a signal to induce heavy ! yrosine phosphorylation of cellular proteins. This rather unusual signal delivery by HgCI2 is diminished by the pre~treatment of cells with phosphatidylinositol-specific phospholipase C, which partially cleaved GPI-anchored proteins from the cell surface. Direct evidence for the involvement of GPI or GPI-anchored proteins in the HgCl2-mediated signaling is provided by the loss ~Df signaling in a mutant thymoma cell line defective in the phosphatidylinositol glycan-class A gene (PIG-A), and its restoration in a transfectant with PIG-A.

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Section: Introductionmentioning

confidence: 99%

Direct evidence of involvement of glycosylphosphatidylinositol‐anchored proteins in the heavy metal‐mediated signal delivery into T lymphocytes

Ohkusu

et al. 1995

FEBS Letters

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“…These purported insulin mediators are inositol-containing phosphoglycans (IPG) produced by phospholipase C (PL-C) hydrolysis of phospholipid-glycans present in B&H1 myocytes [ 11, liver membranes [2] or H35 hepatoma cells [3]. They have been equated to the 'polar head groups' isolated from insulin-treated BCsH 1 myocytes [l] or H35 hepatoma cells [3], which are generated roughly in a 1: 1 ratio to diacylglycerol [ 11. In cell membranes, IPGs are found in phosphatidylinositol-glycans (phospholipid-glycans) and in phosphatidylinositol-glycan-ethanolamine-proteins (henceforth referred to as phospholipid-glycan-proteins) (review [7]). Membrane proteins anchored to the membrane through phospholipid-glycans include 5 ' -nucleotidase and alkaline phosphatase (reviews [8,17]).…”

Section: Introductionmentioning

confidence: 99%

Insulin‐induced decrease in 5′‐nucleotidase activity in skeletal muscle membranes

et al. 1988

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Insulin releases inositol phosphoglycansfrom myocytes in culture [(1986) Science 233,967-9721, which display insulinomimetic activity. Because S'nucleotidase is anchored to the membrane through inositol-containing phospholipid glycans, we investigated whether insulin could release the enzyme from the membrane. Membranes prepared from hindquarter muscles of rats perfused with insulin showed a 23% decrease in S-nucleotidase activity. Isolated membranes from muscle exposed to insulin in vitro also showed a small but reproducible decrease (9%) in S-nucleotidase activity relative to unexposed controls. Phospholipase C from Staphylococcus aureus released m of the membrane-bound S-nucleotidase. We propose that insulin may activate an endogenous phospholipase C that cleaves phospholipid-glycan-anchored proteins.

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“…Coman et al (1944) showed that alterations in membrane metabolism and composition result in phenomena which lead to uncontrolled growth and loss of intracellular communication. Patton and Jensen (1975) showed that metastasis may be directly linked to alterations in cell membranes while other groups showed that phospholipids are important for the immune system's response to tumour growth (Hefta et al, 1988;Low et al, 1988;Freddo et al, 1986).…”

mentioning

confidence: 99%

31P Magnetic resonance phospholipid profiles of neoplastic human breast tissues

Merchant

Meneses²,

Gierke³

et al. 1991

Br J Cancer

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Phospholipids from malignant, benign and noninvolved human breast tissues were extracted by chloroform-methanol (2:1) and analysed by 31P MR spectroscopy at 202.4 MHz. Thirteen phospholipids were identified as constituents of the profiles obtained among the 55 tissue specimens analysed. Observed patterns in phospholipid tissues profiles were distinct, allowing qualitative characterisation of the three tissue groups. Multivariate analysis of lysophosphatidylcholine (LPC) and an uncharacterised phospholipid were shown to be independently significant in predicting benign tissue histology as either fibrocystic disease or fibroadenoma in 92% of cases. Univariate analysis of relative mole-percentage of phosphorus concentrations of individual phospholipids using the ScheffĂ© comparison procedure revealed that in malignant tissues, phosphatidylethanolamine was significantly elevated compared to benign (+ 32%) and noninvolved tissues (+ 22%). Phosphatidylinositol (+ 33%) and phosphatidylcholine plasmalogen (PC plas) (+ 25%) were increased in malignant compared to benign and LPC was decreased (-44%) in malignant compared to noninvolved. LPC was significantly depressed (-39%) in benign tissue compared to normal. Phospholipid indices computed to further characterise the three tissue groups showed PC plas/PC elevated in malignant tissue compared to benign and PE plas/PE depressed in malignant tissue compared to noninvolved. These findings support previous investigations reporting that the alkyl-phospholipid analogues of phosphatidylcholine are released by malignant tissues and that levels of ethanolamine are elevated in malignant tissues. Indices describing the choline-containing phospholipids showed that these lipids are depressed significantly in malignant tissue relative to healthy tissue.

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Structural and Functional Roles of Glycosyl-Phosphatidylinositol in Membranes

Cited by 947 publications

References 150 publications

Direct evidence of involvement of glycosylphosphatidylinositol‐anchored proteins in the heavy metal‐mediated signal delivery into T lymphocytes

Direct evidence of involvement of glycosylphosphatidylinositol‐anchored proteins in the heavy metal‐mediated signal delivery into T lymphocytes

Insulin‐induced decrease in 5′‐nucleotidase activity in skeletal muscle membranes

31P Magnetic resonance phospholipid profiles of neoplastic human breast tissues

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