Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity

Y. Kawakami, T. Miura, R. Bissonnette, D. Hata, Wasif Khan, T. Kitamura, M. Maeda- Yamamoto, S. E. Hartman, L. Yao, F. W. Alt, T. Kawakami

Research output: Contribution to journalArticle

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Abstract

Mast cells derived from Bruton's tyrosine kinase (Btk)-defective xid or btk null mice showed greater expansion in culture containing interleukin-3 (IL-3) than those from wild-type (wt) mice. Although the proliferative response to IL-3 was not significantly different between the wt and xid mast cells, xid and btk null mast cells died by apoptosis more slowly than their wt counterparts upon IL-3 deprivation. Consistent with these findings, the apoptosis-linked c-Jun N-terminal kinase/stress-activated protein kinase (JNK) activity was compromised in these btk-mutated cells upon FcεRI crosslinking or upon stimulation with IL-3 or with stem cell factor. p38 activity was less severely, but significantly, affected by btk mutation, whereas extracellular signal-regulated kinases were not affected by the same mutation. Btk-mediated regulation of apoptosis and JNK activity was confirmed by reconstitution of btk null mutant mast cells with the wt btk cDNA. Furthermore, growth factor withdrawal induced the activation and sustained activity of JNK in wt mast cells, while JNK activity was consistently lower in btk-mutated mast cells. These results support the notion that Btk regulates apoptosis through the JNK activation.

Original languageEnglish
Pages (from-to)3938-3942
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number8
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

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MAP Kinase Kinase 4
Mast Cells
Interleukin-3
Apoptosis
Null Lymphocytes
Mutation
Stem Cell Factor
JNK Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Heat-Shock Proteins
Protein Kinases
Agammaglobulinaemia tyrosine kinase
Intercellular Signaling Peptides and Proteins
Complementary DNA

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. / Kawakami, Y.; Miura, T.; Bissonnette, R.; Hata, D.; Khan, Wasif; Kitamura, T.; Maeda- Yamamoto, M.; Hartman, S. E.; Yao, L.; Alt, F. W.; Kawakami, T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 8, 01.01.1997, p. 3938-3942.

Research output: Contribution to journalArticle

Kawakami, Y, Miura, T, Bissonnette, R, Hata, D, Khan, W, Kitamura, T, Maeda- Yamamoto, M, Hartman, SE, Yao, L, Alt, FW & Kawakami, T 1997, 'Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity', Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 8, pp. 3938-3942. https://doi.org/10.1073/pnas.94.8.3938
Kawakami, Y. ; Miura, T. ; Bissonnette, R. ; Hata, D. ; Khan, Wasif ; Kitamura, T. ; Maeda- Yamamoto, M. ; Hartman, S. E. ; Yao, L. ; Alt, F. W. ; Kawakami, T. / Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. In: Proceedings of the National Academy of Sciences of the United States of America. 1997 ; Vol. 94, No. 8. pp. 3938-3942.
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