TY - JOUR
T1 - Activation of the IκBα kinase complex by MEKK1, a kinase of the JNK pathway
AU - Lee, Frank S.
AU - Hagler, Jeremiah
AU - Chen, Zhijian J.
AU - Maniatis, Tom
N1 - Funding Information:
Correspondence should be addressed to T. M. We thank Drs. Roger Davis and Dean Ballard for gifts of plasmids. We also thank members of the Maniatis laboratory for helpful discussions and critical readings of the manuscript. F. S. L. was supported by National Institutes of Health K08 grant AI01241 and by a Postdoctoral Research Fellowship for Physicians from the Howard Hughes Medical Institute. J. H. was supported by a postdoctoral fellowship from the American Cancer Society (PF-4053). This work was supported by National Institutes of Health grant AI20642 to T. M. and by ProScript, Inc.
PY - 1997/1/24
Y1 - 1997/1/24
N2 - Both NF-κB and c-Jun are activated by cytokines such as TNF-α and by stresses such as UV irradiation. A key step in the activation of NF-κB is the phosphorylation of its inhibitor, IκBα, by a ubiquitination-inducible multiprotein kinase complex (IκBα kinase). A central kinase in the c-Jun activation pathway is mitogen-activated protein kinase/ERK kinase kinase-1 (MEKK1). Here, we show that MEKK1 induces the site-specific phosphorylation of IκBα in vivo and, most strikingly, can directly activate the IκBα kinase complex in vitro. Thus, MEKK1 is a critical component of both the c- Jun and NF-κB stress response pathways. Since the IκBα kinase complex can be independently activated by ubiquitination or MEKK1-dependent phosphorylation, it may be an integrator of multiple signal transduction pathways leading to the activation of NF-κB.
AB - Both NF-κB and c-Jun are activated by cytokines such as TNF-α and by stresses such as UV irradiation. A key step in the activation of NF-κB is the phosphorylation of its inhibitor, IκBα, by a ubiquitination-inducible multiprotein kinase complex (IκBα kinase). A central kinase in the c-Jun activation pathway is mitogen-activated protein kinase/ERK kinase kinase-1 (MEKK1). Here, we show that MEKK1 induces the site-specific phosphorylation of IκBα in vivo and, most strikingly, can directly activate the IκBα kinase complex in vitro. Thus, MEKK1 is a critical component of both the c- Jun and NF-κB stress response pathways. Since the IκBα kinase complex can be independently activated by ubiquitination or MEKK1-dependent phosphorylation, it may be an integrator of multiple signal transduction pathways leading to the activation of NF-κB.
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U2 - 10.1016/S0092-8674(00)81842-5
DO - 10.1016/S0092-8674(00)81842-5
M3 - Article
C2 - 9008162
AN - SCOPUS:0031285250
SN - 0092-8674
VL - 88
SP - 213
EP - 222
JO - Cell
JF - Cell
IS - 2
ER -