Format

Send to

Choose Destination
Cell. 1997 Jan 24;88(2):213-22.

Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway.

Author information

1
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

Abstract

Both NF-kappaB and c-Jun are activated by cytokines such as TNF-alpha and by stresses such as UV irradiation. A key step in the activation of NF-kappaB is the phosphorylation of its inhibitor, IkappaB alpha, by a ubiquitination-inducible multiprotein kinase complex (IkappaB alpha 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 IkappaB alpha in vivo and, most strikingly, can directly activate the IkappaB alpha kinase complex in vitro. Thus, MEKK1 is a critical component of both the c-Jun and NF-kappaB stress response pathways. Since the IkappaB alpha 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-kappaB.

PMID:
9008162
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center