Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria

Takeda, Junji; Miyata, Toshio; Kawagoe, Kazuyoshi; Iida, Yuichiro; Endo, Yuichi; Fujita, Teizo; Takahashi, Minoru; Kitani, Teruo; Kinoshita, Taroh

doi:10.1016/0092-8674(93)90250-t

Cited by 947 publications

(530 citation statements)

References 47 publications

Supporting

Mentioning

516

Contrasting

Unclassified

Order By: Relevance

“…Next, we asked whether a mutant of murine thymoma defective in PIG-A, that codes for the enzyme catalysing the early step of GP1 anchor biosynthesis and is functionally defective in the blood of paroxysmal nocturnal hemoglobinuria patients [23,27,28], would respond to HgC12 for protein tyrosine phosphorylation. As shown in Fig.…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

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

View full text Add to dashboard Cite

show abstract

“…Deficiencies in regulator proteins anchored in host cell membranes via a glycophosphatidyl inositol (GPI) group), such as DAF and CD59, elevate sensitivity of erythrocytes to complement lysis. Individuals with a deficiency of these membrane-associated regulators, most frequently due to a deficiency of GPI anchor formation, are prone to paroxysmal nocturnal hemoglobinuria (PNH) (Takeda et al, 1993). PNH is characterised by intravascular destruction of erythrocytes and results in oxygen insufficiency and hemoglobin excretion by the kidneys.…”

Section: Complement Regulators and Receptorsmentioning

confidence: 99%

Complement genetics, deficiencies, and disease associations

Mayilyan

2012

Protein Cell

149

View full text Add to dashboard Cite

The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

show abstract

“…1,2 Affected progeny cells are incapable of biosynthesis of the glycosylphosphatidylinositol (GPI)-anchor and lack from their surface all GPI-anchored proteins (GPI-AP). Intravascular hemolysis results from failure of complement inactivation by CD59, missing from the surface of GPI-AP-deficient erythrocytes.…”

Section: Introductionmentioning

confidence: 99%

Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients

Risitano

Maciejewski²,

Muranski

et al. 2005

Leukemia

View full text Add to dashboard Cite

Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria

Cited by 947 publications

References 47 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

Complement genetics, deficiencies, and disease associations

Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients

Contact Info

Product

Resources

About