Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf.

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf. / Marzec, M.; Kasprzycka, M.; Liu, X.; Raghunath, P. N.; Wlodarski, P.; Wasik, M. A.

In: Oncogene, Vol. 26, No. 6, 2007, p. 813-821.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Marzec, M, Kasprzycka, M, Liu, X, Raghunath, PN, Wlodarski, P & Wasik, MA 2007, 'Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf.', Oncogene, vol. 26, no. 6, pp. 813-821. https://doi.org/10.1038/sj.onc.1209843

APA

Marzec, M., Kasprzycka, M., Liu, X., Raghunath, P. N., Wlodarski, P., & Wasik, M. A. (2007). Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf. Oncogene, 26(6), 813-821. https://doi.org/10.1038/sj.onc.1209843

Vancouver

Marzec M, Kasprzycka M, Liu X, Raghunath PN, Wlodarski P, Wasik MA. Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf. Oncogene. 2007;26(6):813-821. https://doi.org/10.1038/sj.onc.1209843

Author

Marzec, M. ; Kasprzycka, M. ; Liu, X. ; Raghunath, P. N. ; Wlodarski, P. ; Wasik, M. A. / Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf. In: Oncogene. 2007 ; Vol. 26, No. 6. pp. 813-821.

Bibtex

@article{55c699783db7477c97fdabe9b0a416ac,

title = "Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf.",

abstract = "The mechanisms of cell transformation mediated by the highly oncogenic, chimeric NPM/ALK tyrosine kinase remain only partially understood. Here we report that cell lines and native tissues derived from the NPM/ALK-expressing T-cell lymphoma (ALK+ TCL) display phosphorylation of the extracellular signal-regulated protein kinase (ERK) 1/2 complex. Transfection of BaF3 cells with NPM/ALK induces phosphorylation of EKR1/2 and of its direct activator mitogen-induced extracellular kinase (MEK) 1/2. Depletion of NPM/ALK by small interfering RNA (siRNA) or its inhibition by WHI-154 abrogates the MEK1/2 and ERK1/2 phosphorylation. The NPM/ALK-induced MEK/ERK activation is independent of c-Raf as evidenced by the lack of MEK1/2 and ERK1/2 phosphorylation upon c-Raf inactivation by two different inhibitors, RI and ZM336372, and by its siRNA-mediated depletion. In contrast, ERK1/2 activation is strictly MEK1/2 dependent as shown by suppression of the ERK1/2 phosphorylation by the MEK1/2 inhibitor U0126. The U0126-mediated inhibition of ERK1/2 activation impaired proliferation and viability of the ALK+ TCL cells and expression of anti-apoptotic factor Bcl-xL and cell cycle-promoting CDK4 and phospho-RB. Finally, siRNA-mediated depletion of both ERK1 and ERK2 inhibited cell proliferation, whereas depletion of ERK 1 (but not ERK2) markedly increased cell apoptosis. These findings identify MEK/ERK as a new signaling pathway activated by NPM/ALK and indicate that the pathway represents a novel therapeutic target in the ALK-induced malignancies. [on SciFinder(R)]",

keywords = "NPM ALK kinase MEK ERK signaling T cell lymphoma",

author = "M. Marzec and M. Kasprzycka and X. Liu and Raghunath, {P. N.} and P. Wlodarski and Wasik, {M. A.}",

year = "2007",

doi = "10.1038/sj.onc.1209843",

language = "English",

volume = "26",

pages = "813--821",

journal = "Oncogene",

issn = "0950-9232",

publisher = "nature publishing group",

number = "6",

}

RIS

TY - JOUR

T1 - Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf.

AU - Marzec, M.

AU - Kasprzycka, M.

AU - Liu, X.

AU - Raghunath, P. N.

AU - Wlodarski, P.

AU - Wasik, M. A.

PY - 2007

Y1 - 2007

N2 - The mechanisms of cell transformation mediated by the highly oncogenic, chimeric NPM/ALK tyrosine kinase remain only partially understood. Here we report that cell lines and native tissues derived from the NPM/ALK-expressing T-cell lymphoma (ALK+ TCL) display phosphorylation of the extracellular signal-regulated protein kinase (ERK) 1/2 complex. Transfection of BaF3 cells with NPM/ALK induces phosphorylation of EKR1/2 and of its direct activator mitogen-induced extracellular kinase (MEK) 1/2. Depletion of NPM/ALK by small interfering RNA (siRNA) or its inhibition by WHI-154 abrogates the MEK1/2 and ERK1/2 phosphorylation. The NPM/ALK-induced MEK/ERK activation is independent of c-Raf as evidenced by the lack of MEK1/2 and ERK1/2 phosphorylation upon c-Raf inactivation by two different inhibitors, RI and ZM336372, and by its siRNA-mediated depletion. In contrast, ERK1/2 activation is strictly MEK1/2 dependent as shown by suppression of the ERK1/2 phosphorylation by the MEK1/2 inhibitor U0126. The U0126-mediated inhibition of ERK1/2 activation impaired proliferation and viability of the ALK+ TCL cells and expression of anti-apoptotic factor Bcl-xL and cell cycle-promoting CDK4 and phospho-RB. Finally, siRNA-mediated depletion of both ERK1 and ERK2 inhibited cell proliferation, whereas depletion of ERK 1 (but not ERK2) markedly increased cell apoptosis. These findings identify MEK/ERK as a new signaling pathway activated by NPM/ALK and indicate that the pathway represents a novel therapeutic target in the ALK-induced malignancies. [on SciFinder(R)]

AB - The mechanisms of cell transformation mediated by the highly oncogenic, chimeric NPM/ALK tyrosine kinase remain only partially understood. Here we report that cell lines and native tissues derived from the NPM/ALK-expressing T-cell lymphoma (ALK+ TCL) display phosphorylation of the extracellular signal-regulated protein kinase (ERK) 1/2 complex. Transfection of BaF3 cells with NPM/ALK induces phosphorylation of EKR1/2 and of its direct activator mitogen-induced extracellular kinase (MEK) 1/2. Depletion of NPM/ALK by small interfering RNA (siRNA) or its inhibition by WHI-154 abrogates the MEK1/2 and ERK1/2 phosphorylation. The NPM/ALK-induced MEK/ERK activation is independent of c-Raf as evidenced by the lack of MEK1/2 and ERK1/2 phosphorylation upon c-Raf inactivation by two different inhibitors, RI and ZM336372, and by its siRNA-mediated depletion. In contrast, ERK1/2 activation is strictly MEK1/2 dependent as shown by suppression of the ERK1/2 phosphorylation by the MEK1/2 inhibitor U0126. The U0126-mediated inhibition of ERK1/2 activation impaired proliferation and viability of the ALK+ TCL cells and expression of anti-apoptotic factor Bcl-xL and cell cycle-promoting CDK4 and phospho-RB. Finally, siRNA-mediated depletion of both ERK1 and ERK2 inhibited cell proliferation, whereas depletion of ERK 1 (but not ERK2) markedly increased cell apoptosis. These findings identify MEK/ERK as a new signaling pathway activated by NPM/ALK and indicate that the pathway represents a novel therapeutic target in the ALK-induced malignancies. [on SciFinder(R)]

KW - NPM ALK kinase MEK ERK signaling T cell lymphoma

U2 - 10.1038/sj.onc.1209843

DO - 10.1038/sj.onc.1209843

M3 - Journal article

VL - 26

SP - 813

EP - 821

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 6

ER -

ID: 202377089