Overview:

MEKK1 or MEK kinase, is a serine/threonine kinase that is downstream of mitogenic and metabolic stimuli, including insulin and many growth factors. MEKK1 functions not only as an upstream activator of ERK and JNK through its kinase domain, but also as an E3 ligase through its PHD domain, providing a negative regulatory mechanism for decreasing ERK1/ERK2 activity by ubiquitination and degradation (1). MEKK1 -/- embryonic stem cells from mice show loss or altered responses of JNK to microtubule disruption and cold stress (2). Furthermore, activation of JNK is lost and that of ERK is diminished in response to hyperosmolarity and serum factors in MEKK1 -/- cells.

Gene Aliases:

MAP3K1; MEKK; MAPKKK1

Genbank Number:

NM_005921

References:

1. Lu, Z. et al: The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2. Molec. Cell 9: 945-956, 2002.

2. Yujiri, T. et al: Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption. Science 282: 1911-1914, 1998.