Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in lymphocytes.

Research output: Contribution to journalJournal articlepeer-review

  • Monika Kasprzycka
  • Miroslaw Majewski
  • Zhi-Jong Wang
  • Andrzej Ptasznik
  • Maria Wysocka
  • Qian Zhang
  • Marzec, Michal Tomasz
  • Phyllis Gimotty
  • Mark R. Crompton
  • Mariusz A. Wasik
Tyrosine kinases play a fundamental role in cell proliferation, survival, adhesion, and motility and have also been shown to mediate malignant cell transformation. Here we describe constitutive expression of the protein tyrosine kinase Brk in a large proportion of cutaneous T-cell lymphomas and other transformed T- and B-cell populations. The kinase is expressed in the nuclear localization and activated state. Brk expression was also induced in normal T cells on their activation. Introduced expression of the Brk gene resulted in markedly diminished cytokine and growth factor dependence of transfected BaF3 lymphocytes in regard to their in vitro proliferation and survival. Brk also conferred in vivo oncogenicity on the BaF3 cells. SiRNA-mediated inhibition of the endogenous Brk in malignant T cells diminished their growth and survival capacity. These findings document inducible expression of Brk in normal T lymphocytes and persistent expression of the activated kinase in malignant T and B cells. Furthermore, our results indicate that Brk may play a key role in lymphomagenesis, hence identifying the kinase as a potential therapeutic target in lymphomas. [on SciFinder(R)]
Original languageEnglish
JournalAmerican Journal of Pathology
Volume168
Issue number5
Pages (from-to)1631-1641
Number of pages11
ISSN0002-9440
DOIs
Publication statusPublished - 2006
Externally publishedYes

Bibliographical note

M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.

CAPLUS AN 2006:499467(Journal)

    Research areas

  • Brk IL3 T B cell lymphoma

ID: 202375956