BTK as a Mediator of Radiation-Induced Apoptosis in DT-40 Lymphoma B Cells

Uckun, Fatih M.; Waddick, Kevin G.; Mahajan, Sandeep; Xiao, Jun; Takata, Minoru; Bolen, Joseph B.; Kurosaki, Tomohiro

doi:10.1126/science.273.5278.1096

Cited by 153 publications

(175 citation statements)

References 69 publications

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“…Targeted disruption of Btk has been shown to lead the B cells toward apoptosis (Anderson et al, 1996) and overexpression of Btk in chicken B cells suppresses the Fas-mediated apoptotic signal via the disruption of the FAS-FADD interaction. By contrast, Btk has also been demonstrated to induce apoptosis in HeLa cells (Islam et al, 2000) and to mediate the radiation-induced apoptosis in DT-40 lymphoma B-cells (Uckun et al, 1996). Our findings reported here, that Etk sensitizes MDA-MB-468 cells toward EGF-induced apoptosis, provide additional evidence that Tec family kinases are involved in proapoptotic functions.…”

Section: Discussionsupporting

confidence: 60%

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

et al. 2003

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Section: Discussionsupporting

confidence: 60%

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

et al. 2003

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“…In contrast, genistein but not PD98059 suppressed DNA fragmentation induced by g irradiation (data not shown). A similar inhibition of g irradiationinduced apoptosis by genistein has been observed in a di erent system (Uckun et al, 1996). When we examined e ects of PD98059 on hGM-CSF dependent prevention of g irradiation-induced apoptosis, we found this activity was never a ected in the presence of PD98059 ( Figure 4a).…”

Section: Levels Of P53 Bax and Bcl-x Lsupporting

confidence: 79%

Analysis of mechanisms involved in the prevention of γ irradiation-induced apoptosis by hGM-CSF

Liu

Mohi

et al. 2000

Oncogene

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Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces proliferation and sustains viability of the mouse interleukin (IL)-3 dependent lymphoid cell line BA/F3 expressing the hGM-CSF receptor. Caspase-3 like enzyme activity and DNA fragmentation were augmented by depletion of this factor from the cell, and exposure to g irradiation accelerated kinetics of these events. Anti g irradiationinduced apoptosis occurred through various mutant GM-CSF receptors and only the box1 region was essential while the C terminal region, including tyrosine residues which are required for MAPK cascade activation, was dispensable. Consistent with this notion, the addition of PD98059 had no e ect on this activity thereby indicating that activation of MAPK is not essential for the activity. As expected, g irradiation increased p53 protein and bax mRNA levels and the presence of hGM-CSF dramatically modulated bax/bcl-X L ratio. The PI-3K speci®c inhibitor wortmannin did not a ect hGM-CSF dependent anti g irradiation induced apoptosis nor bcl-X L induction, thus bcl-X L but not PI-3K pathway seems to be involved in hGM-CSF dependent anti g irradiation-induced apoptosis. It is well documented that the box1 region is essential for GM-CSF dependent activation of JAK2 and JAK2 speci®c inhibitor AG490 suppressed anti g irradiation-induced apoptosis by hGM-CSF. An arti®cial JAK2 activating molecule in which extracellular and the transmembrane of bc fused with whole JAK2 can sustain BA/F3 cells survival and proliferation mIL-3 independently, but these cells are susceptible to g irradiation. Furthermore GyrB/Jak2, which can activate STAT5 but not the MAPK cascade nor survival of BA/F3 cells, also could not prevent g irradiation-induced apoptosis. Although JAK2 is essential for hGM-CSF dependent anti g irradiation-induced apoptosis, it appeared that JAK2 does not seem su cient for the activity. Oncogene (2000) 19, 571 ± 579.

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“…Apoptosis induction in U937 cells was also abrogated by HMA (Ginestier-Verne et al, 1996). PTKs have been implicated in the triggering of apoptosis in some cellular contexts (Carson et al, 1994;Bergamaschi et al, 1993;Uckun et al, 1992;Uckun et al, 1996) while promoting survival in others (Bedi et al, 1994;McGahon et al, 1994;Zhu et al, 1996). It is therefore plausible that an HMA-sensitive PTK is part of the signalling pathway which induces apoptosis in HL60 and U937 cells following etoposide treatment.…”

Section: Discussionmentioning

confidence: 99%

Herbimycin A accelerates the induction of apoptosis following etoposide treatment or γ-irradiation of bcr/abl-positive leukaemia cells

et al. 1998

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Philadelphia chromosome (Ph)-positive leukaemia cells express the chimeric bcr/abl oncoprotein, whose deregulated protein tyrosine kinase (PTK) activity antagonizes the induction of apoptosis by DNA damaging agents. Treatment of Ph-positive K562, TOM 1 and KCL-22 cells with etoposide for 2d induced cytosolic vacuolation, but not nuclear condensation or DNA fragmentation. The bcr/abl kinase-selective inhibitor herbimycin A increased the induction of nuclear apoptosis by etoposide or g-radiation. The concentration of herbimycin required to synergize with etoposide was similar to that required to decrease the level of tyrosine phosphorylated proteins or of the protein tyrosine kinase activity of anti-abl immune complexes in K562 cells. The ability of herbimycin A to sensitize K562, TOM 1 or KCL-22 cells to apoptosis induction correlated with its ability to decrease the cellular content of phosphotyrosyl proteins in these Philadelphia-positive lines. Enhancement of nuclear apoptosis by herbimycin was not attributable to downregulation of the bcl-2 or bcl-X L anti-apoptotic proteins. In contrast, herbimycin protected Philadelphianegative HL60 cells from apoptosis induction by etoposide and did not a ect killing of NC37 and CEM cells. The data suggest that the induction of apoptosis is blocked in cells expressing the bcr/abl oncoprotein and that herbimycin A increases induction of programmed cell death following DNA damage. Selective PTK inhibitors may therefore be of value in securing the genetic death of Ph-positive leukaemia cells.

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BTK as a Mediator of Radiation-Induced Apoptosis in DT-40 Lymphoma B Cells

Cited by 153 publications

References 69 publications

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

Analysis of mechanisms involved in the prevention of γ irradiation-induced apoptosis by hGM-CSF

Herbimycin A accelerates the induction of apoptosis following etoposide treatment or γ-irradiation of bcr/abl-positive leukaemia cells

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