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

Yuko Kawakami, Toru Miura, Reid Bissonnette, Daisuke Hata, Wasif N. Khan, Toshio Kitamura, Mari Maeda-Yamamoto, Stephen E. Hartman, Libo Yao, Frederick W. Alt, Toshiaki Kawakami

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

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 (US)
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 - Apr 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • General

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