Involvement of Wiskott-Aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway

Yoshihiro Baba, Shigeaki Nonoyama, Masato Matsushita, Tomoki Yamadori, Shoji Hashimoto, Kohsuke Imai, Shigeyuki Arai, Toshio Kunikata, Masashi Kurimoto, Tomohiro Kurosaki, Hans D. Ochs, Jun Ichi Yata, Tadamitsu Kishimoto, Satoshi Tsukada

Research output: Contribution to journalArticle

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Abstract

Bruton's tyrosine kinase (Btk) has been shown to play a role in normal B-lymphocyte development. Defective expression of Btk leads to human and murine immunodeficiencies. However, the exact role of Btk in the cytoplasmic signal transduction in B cells is still unclear. This study represents a search for the substrate for Btk in vivo. We identified one of the major phosphoproteins associated with Btk in the preB cell line NALM6 as the Wiskott-Aldrich syndrome protein (WASP), the gene product responsible for Wiskott-Aldrich syndrome, which is another hereditary immunodeficiency with distinct abnormalities in hematopoietic cells. We demonstrated that WASP was transiently tyrosine-phosphorylated after B-cell antigen receptor cross- linking on B cells, suggesting that WASP is located downstream of cytoplasmic tyrosine kinases. An in vivo reconstitution system demonstrated that WASP is physically associated with Btk and can serve as the substrate for Btk. A protein binding assay suggested that the tyrosine-phosphorylation of WASP alters the association between WASP and a cellular protein. Furthermore, identification of the phosphorylation site of WASP in reconstituted cells allowed us to evaluate the catalytic specificity of Btk, the exact nature of which is still unknown.

Original languageEnglish
Pages (from-to)2003-2012
Number of pages10
JournalBlood
Volume93
Issue number6
Publication statusPublished - Mar 15 1999
Externally publishedYes

Fingerprint

Wiskott-Aldrich Syndrome Protein
Protein-Tyrosine Kinases
B-Lymphocytes
Cells
Phosphorylation
Tyrosine
Wiskott-Aldrich Syndrome
Signal transduction
B-Cell Antigen Receptors
Lymphocytes
Agammaglobulinaemia tyrosine kinase
IgA receptor
Phosphoproteins
Substrates
Protein Binding
Crosslinking
Assays
Signal Transduction
Proteins
Association reactions

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Baba, Y., Nonoyama, S., Matsushita, M., Yamadori, T., Hashimoto, S., Imai, K., ... Tsukada, S. (1999). Involvement of Wiskott-Aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway. Blood, 93(6), 2003-2012.

Involvement of Wiskott-Aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway. / Baba, Yoshihiro; Nonoyama, Shigeaki; Matsushita, Masato; Yamadori, Tomoki; Hashimoto, Shoji; Imai, Kohsuke; Arai, Shigeyuki; Kunikata, Toshio; Kurimoto, Masashi; Kurosaki, Tomohiro; Ochs, Hans D.; Yata, Jun Ichi; Kishimoto, Tadamitsu; Tsukada, Satoshi.

In: Blood, Vol. 93, No. 6, 15.03.1999, p. 2003-2012.

Research output: Contribution to journalArticle

Baba, Y, Nonoyama, S, Matsushita, M, Yamadori, T, Hashimoto, S, Imai, K, Arai, S, Kunikata, T, Kurimoto, M, Kurosaki, T, Ochs, HD, Yata, JI, Kishimoto, T & Tsukada, S 1999, 'Involvement of Wiskott-Aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway', Blood, vol. 93, no. 6, pp. 2003-2012.
Baba Y, Nonoyama S, Matsushita M, Yamadori T, Hashimoto S, Imai K et al. Involvement of Wiskott-Aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway. Blood. 1999 Mar 15;93(6):2003-2012.
Baba, Yoshihiro ; Nonoyama, Shigeaki ; Matsushita, Masato ; Yamadori, Tomoki ; Hashimoto, Shoji ; Imai, Kohsuke ; Arai, Shigeyuki ; Kunikata, Toshio ; Kurimoto, Masashi ; Kurosaki, Tomohiro ; Ochs, Hans D. ; Yata, Jun Ichi ; Kishimoto, Tadamitsu ; Tsukada, Satoshi. / Involvement of Wiskott-Aldrich syndrome protein in B-cell cytoplasmic tyrosine kinase pathway. In: Blood. 1999 ; Vol. 93, No. 6. pp. 2003-2012.
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