MAP3K1 / MEKK1

mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase

MEKK1, a MAP3K type protein kinase, is a member of the stress-activated protein kinase (SAPK) pathways which convey pro-apoptotic signals. The protein consists of a C-terminal protein kinase domain and an extensive N-terminal domain that includes two proline-rich segments containing putative binding sites for proteins with SH3 domains, a consensus binding site for 14-3-3 proteins, two PH domains and an acid rich motif with two sites for cleavage by proapoptotic caspase cysteine proteases. MEKK1 activates MKK4/MAP2K4 and, to a lesser extent, MKK7/MAP2K7 in the SAPK cascade. MEKK1 also has been shown to activate the transcription factor CCAAT/enhancer-binding protein-beta-dependent gene expression via MEK1-ERK1/2 kinases in response to IFN-gamma. In MEKK1 (-/-) mouse embryonic stem cells the response of JNK to microtubule disruption, cold stress, hyperosmolarity and serum factors is lost or altered, and the response of ERK to hyperosmolarity and serum factors is diminished.

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