X‐Linked Agammaglobulinemia and Other Immunoglobulin Deficiencies

Smith, C. I. Edvard; Islam, Khalid B.; Vořechovský, Igor; Olerup, Olle; Wallin, Erik; Rabbani, Hodjattallah; Baskin, Berivan; Hammarström, Lennart

doi:10.1111/j.1600-065x.1994.tb00851.x

Cited by 115 publications

(81 citation statements)

References 109 publications

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“…BTK has a pleckstrin homology (PH) domain, a TEC homology domain, a single SH3 domain, a single SH2 domain, and a catalytic kinase domain (12,13,17,30). Mutations in the SH2 domain as well as PH domain of the BTK result in defective B-cell development, leading to human Xlinked agammaglobulinemia (16,(31)(32)(33)(34). The PH domain is responsible for interactions with various isoforms of protein kinase C,␤␥ subunits of heterotrimeric GTP-binding proteins and phosphatidylinositol-4,5-bisphosphate, the precursor to Ins-1,4,5-P 3 (35)(36)(37)(38).…”

Section: Fig 2 Emf-induced Btk Activation Of Btk-deficient Dt40mentioning

confidence: 99%

Electromagnetic Field-induced Stimulation of Bruton's Tyrosine Kinase

Kristupaitis¹,

Dıbırdık²,

Vassilev³

et al. 1998

Journal of Biological Chemistry

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Section: Fig 2 Emf-induced Btk Activation Of Btk-deficient Dt40mentioning

confidence: 99%

Electromagnetic Field-induced Stimulation of Bruton's Tyrosine Kinase

Kristupaitis¹,

Dıbırdık²,

Vassilev³

et al. 1998

Journal of Biological Chemistry

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“…ruton's tyrosine kinase (Btk) 3 is a cytoplasmic protein tyrosine kinase (PTK) expressed in all hemopoietic cell lineages except for T lymphocytes and plasma cells (1,2). Btk is expressed at all stages of B lineage development, before plasma cells, starting from CD34 ϩ pro-B to mature B cells (3).…”

mentioning

confidence: 99%

“…In the mouse, this effect is exerted at two stages, first during the transition from small pre-B cells to immature B cells in the bone marrow, and later during the maturation from IgD low IgM high to IgD high IgM low stages in the periphery (4). Btk belongs to the Tec family of PTKs, which all contain five domains: pleckstrin homology, Tec homology, SH3 and SH2, and kinase (SH1) domains (1,5). Btk is the defective gene in XLA, a hereditary immunodeficiency disease (6,7) caused by a block in early B cell development (8 -11).…”

mentioning

confidence: 99%

Six X-Linked Agammaglobulinemia-Causing Missense Mutations in the Src Homology 2 Domain of Bruton’s Tyrosine Kinase: Phosphotyrosine-Binding and Circular Dichroism Analysis

Mattsson

Lappalainen

Backesjo

et al. 2000

The Journal of Immunology

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Src homology 2 (SH2) domains recognize phosphotyrosine (pY)-containing sequences and thereby mediate their association to ligands. Bruton’s tyrosine kinase (Btk) is a cytoplasmic protein tyrosine kinase, in which mutations cause a hereditary immunodeficiency disease, X-linked agammaglobulinemia (XLA). Mutations have been found in all Btk domains, including SH2. We have analyzed the structural and functional effects of six disease-related amino acid substitutions in the SH2 domain: G302E, R307G, Y334S, L358F, Y361C, and H362Q. Also, we present a novel Btk SH2 missense mutation, H362R, leading to classical XLA. Based on circular dichroism analysis, the conformation of five of the XLA mutants studied differs from the native Btk SH2 domain, while mutant R307G is structurally identical. The binding of XLA mutation-containing SH2 domains to pY-Sepharose was reduced, varying between 1 and 13% of that for the native SH2 domain. The solubility of all the mutated proteins was remarkably reduced. SH2 domain mutations were divided into three categories: 1) Functional mutations, which affect residues presumably participating directly in pY binding (R307G); 2) structural mutations that, via conformational change, not only impair pY binding, but severely derange the structure of the SH2 domain and possibly interfere with the overall conformation of the Btk molecule (G302E, Y334S, L358F, and H362Q); and 3) structural-functional mutations, which contain features from both categories above (Y361C).

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“…In patients with XLA, B cell development and immunoglobulin synthesis were defective because of impaired B cell receptor (BCR) signaling. 33,34) Cross-linking of BCR leads to the activation of Src family kinases, which in turn phosphorylate Btk. Phosphopeptide mapping and mutational analyses of Btk have identified 551 tyrosine as the transphosphorylation site by Src family kinases.…”

Section: Discussionmentioning

confidence: 99%