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Science 4 December 1998:
Vol. 282. no. 5395, pp. 1911 - 1914
DOI: 10.1126/science.282.5395.1911
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Reports

Role of MEKK1 in Cell Survival and Activation of JNK and ERK Pathways Defined by Targeted Gene Disruption

Toshiaki Yujiri, Susan Sather, Gary R. Fanger, Gary L. Johnson *

Targeted disruption of the gene encoding MEK kinase 1 (MEKK1), a mitogen-activated protein kinase (MAPK) kinase kinase, defined its function in the regulation of MAPK pathways and cell survival. MEKK1-/- embryonic stem cells from mice had lost or altered responses of the c-Jun amino-terminal kinase (JNK) to microtubule disruption and cold stress but activated JNK normally in response to heat shock, anisomycin, and ultraviolet irradiation. Activation of JNK was lost and that of extracellular signal-regulated protein kinase (ERK) was diminished in response to hyperosmolarity and serum factors in MEKK1-/- cells. Loss of MEKK1 expression resulted in a greater apoptotic response of cells to hyperosmolarity and microtubule disruption. When activated by specific stresses that alter cell shape and the cytoskeleton, MEKK1 signals to protect cells from apoptosis.

Program in Molecular Signal Transduction, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO 80206, USA, and the Department of Pharmacology, University of Colorado Medical School, Denver, CO 80262, USA.
*   To whom correspondence should be addressed. E-mail: johnsong{at}njc.org

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R. H. See, D. Calvo, Y. Shi, H. Kawa, M. P.-S. Luke, Z. Yuan, and Y. Shi (2001)
J. Biol. Chem. 276, 16310-16317
   Abstract »    Full Text »    PDF »
Role of Receptor-interacting Protein in Tumor Necrosis Factor-alpha -dependent MEKK1 Activation.
J. W. Kim, C. O. Joe, and E.-J. Choi (2001)
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Phosphorylation of the Tumor Necrosis Factor Receptor CD120a (p55) Recruits Bcl-2 and Protects against Apoptosis.
V. Cottin, A. A. Van Linden, and D. W. H. Riches (2001)
J. Biol. Chem. 276, 17252-17260
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Cellular Stress Regulates the Nucleocytoplasmic Distribution of the Protein-tyrosine Phosphatase TCPTP.
M. H. C. Lam, B. J. Michell, M. T. Fodero-Tavoletti, B. E. Kemp, N. K. Tonks, and T. Tiganis (2001)
J. Biol. Chem. 276, 37700-37707
   Abstract »    Full Text »    PDF »
MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.
T. Yujiri, M. Ware, C. Widmann, R. Oyer, D. Russell, E. Chan, Y. Zaitsu, P. Clarke, K. Tyler, Y. Oka, et al. (2000)
PNAS 97, 7272-7277
   Abstract »    Full Text »    PDF »


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