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Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain.

Mohamed, Abdalla J; Yu, Liang; Bäckesjö, Carl-Magnus; Vargas, Leonardo; Faryal, Rani; Aints, Alar; Christensson, Birger; Berglöf, Anna; Vihinen, Mauno LU and Nore, Beston F, et al. (2009) In Immunological Reviews 228(1). p.58-73
Abstract
Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases. Mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Activation of Btk triggers a cascade of signaling events that culminates in the generation of calcium mobilization and fluxes, cytoskeletal rearrangements, and transcriptional regulation involving nuclear factor-kappaB (NF-kappaB) and nuclear factor of activated T cells (NFAT). In B cells, NF-kappaB was shown to bind to the Btk promoter and induce transcription, whereas the B-cell receptor-dependent NF-kappaB signaling... (More)
Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases. Mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Activation of Btk triggers a cascade of signaling events that culminates in the generation of calcium mobilization and fluxes, cytoskeletal rearrangements, and transcriptional regulation involving nuclear factor-kappaB (NF-kappaB) and nuclear factor of activated T cells (NFAT). In B cells, NF-kappaB was shown to bind to the Btk promoter and induce transcription, whereas the B-cell receptor-dependent NF-kappaB signaling pathway requires functional Btk. Moreover, Btk activation is tightly regulated by a plethora of other signaling proteins including protein kinase C (PKC), Sab/SH3BP5, and caveolin-1. For example, the prolyl isomerase Pin1 negatively regulates Btk by decreasing tyrosine phosphorylation and steady state levels of Btk. It is intriguing that PKC and Pin1, both of which are negative regulators, bind to the pleckstrin homology domain of Btk. To this end, we describe here novel mutations in the pleckstrin homology domain investigated for their transforming capacity. In particular, we show that the mutant D43R behaves similar to E41K, already known to possess such activity. (Less)
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keywords
Agammaglobulinemia: immunology, Neoplasms: metabolism, Protein-Tyrosine Kinases: chemistry, Protein-Tyrosine Kinases: immunology, Protein-Tyrosine Kinases: metabolism, X-Linked Combined Immunodeficiency Diseases: immunology
in
Immunological Reviews
volume
228
issue
1
pages
58 - 73
publisher
Munksgaard International Publishers
external identifiers
  • PMID:19290921
  • Scopus:61849183478
ISSN
1600-065X
DOI
10.1111/j.1600-065X.2008.00741.x
language
English
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no
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29f844e2-9c8d-4bb2-b5b3-5623a55e3242 (old id 3634940)
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http://www.ncbi.nlm.nih.gov/pubmed/19290921?dopt=Abstract
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2013-06-12 20:35:27
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2016-11-20 04:21:19
@misc{29f844e2-9c8d-4bb2-b5b3-5623a55e3242,
  abstract     = {Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases. Mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Activation of Btk triggers a cascade of signaling events that culminates in the generation of calcium mobilization and fluxes, cytoskeletal rearrangements, and transcriptional regulation involving nuclear factor-kappaB (NF-kappaB) and nuclear factor of activated T cells (NFAT). In B cells, NF-kappaB was shown to bind to the Btk promoter and induce transcription, whereas the B-cell receptor-dependent NF-kappaB signaling pathway requires functional Btk. Moreover, Btk activation is tightly regulated by a plethora of other signaling proteins including protein kinase C (PKC), Sab/SH3BP5, and caveolin-1. For example, the prolyl isomerase Pin1 negatively regulates Btk by decreasing tyrosine phosphorylation and steady state levels of Btk. It is intriguing that PKC and Pin1, both of which are negative regulators, bind to the pleckstrin homology domain of Btk. To this end, we describe here novel mutations in the pleckstrin homology domain investigated for their transforming capacity. In particular, we show that the mutant D43R behaves similar to E41K, already known to possess such activity.},
  author       = {Mohamed, Abdalla J and Yu, Liang and Bäckesjö, Carl-Magnus and Vargas, Leonardo and Faryal, Rani and Aints, Alar and Christensson, Birger and Berglöf, Anna and Vihinen, Mauno and Nore, Beston F and Smith, C I Edvard},
  issn         = {1600-065X},
  keyword      = {Agammaglobulinemia: immunology,Neoplasms: metabolism,Protein-Tyrosine Kinases: chemistry,Protein-Tyrosine Kinases: immunology,Protein-Tyrosine Kinases: metabolism,X-Linked Combined Immunodeficiency Diseases: immunology},
  language     = {eng},
  number       = {1},
  pages        = {58--73},
  publisher    = {ARRAY(0xa0f98a0)},
  series       = {Immunological Reviews},
  title        = {Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain.},
  url          = {http://dx.doi.org/10.1111/j.1600-065X.2008.00741.x},
  volume       = {228},
  year         = {2009},
}