TY - JOUR
T1 - Signal transduction pathways regulated by mitogen-activated/extracellular response kinase kinase kinase induce cell death
AU - Johnson, Nancy Lassignal
AU - Gardner, Anne M.
AU - Diener, Katrina M.
AU - Lange-Carter, Carol A.
AU - Gleavy, Janice
AU - Jarpe, Matthew B.
AU - Minden, Audrey
AU - Karin, Michael
AU - Zon, Leonard I.
AU - Johnson, Gary L.
PY - 1996/2/9
Y1 - 1996/2/9
N2 - Mitogen-activated/extracellular response kinase kinase (MEK) kinase (MEKK) is a serine-threonine kinase that regulates sequential protein phosphorylation pathways, leading to the activation of mitogen-activated protein kinases (MAPK), including members of the Jun kinase (JNK)/stress- activated protein kinase (SAPK) family. In Swiss 3T3 and REF52 fibroblasts, activated MEKK induces cell death involving cytoplasmic shrinkage, nuclear condensation, and DNA fragmentation characteristic of apoptosis. Expression of activated MEKK enhanced the apoptotic response to ultraviolet irradiation, indicating that MEKK-regulated pathways sensitize cells to apoptotic stimuli. Inducible expression of activated MEKK stimulated the transactivation of c- Myc and Elk-1. Activated Raf, the serine-threonine protein kinase that activates the ERK members of the MAPK family, stimulated Elk-1 transactivation but not c-Myc; expression of activated Raf does not induce any of the cellular changes associated with MEKK-mediated cell death. Thus, MEKK selectively regulates signal transduction pathways that contribute to the apoptotic response.
AB - Mitogen-activated/extracellular response kinase kinase (MEK) kinase (MEKK) is a serine-threonine kinase that regulates sequential protein phosphorylation pathways, leading to the activation of mitogen-activated protein kinases (MAPK), including members of the Jun kinase (JNK)/stress- activated protein kinase (SAPK) family. In Swiss 3T3 and REF52 fibroblasts, activated MEKK induces cell death involving cytoplasmic shrinkage, nuclear condensation, and DNA fragmentation characteristic of apoptosis. Expression of activated MEKK enhanced the apoptotic response to ultraviolet irradiation, indicating that MEKK-regulated pathways sensitize cells to apoptotic stimuli. Inducible expression of activated MEKK stimulated the transactivation of c- Myc and Elk-1. Activated Raf, the serine-threonine protein kinase that activates the ERK members of the MAPK family, stimulated Elk-1 transactivation but not c-Myc; expression of activated Raf does not induce any of the cellular changes associated with MEKK-mediated cell death. Thus, MEKK selectively regulates signal transduction pathways that contribute to the apoptotic response.
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U2 - 10.1074/jbc.271.6.3229
DO - 10.1074/jbc.271.6.3229
M3 - Article
C2 - 8621725
AN - SCOPUS:0000154443
SN - 0021-9258
VL - 271
SP - 3229
EP - 3237
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -