Kinase Subfamily nmo

Kinase Classification: Group CMGC: Family MAPK: Subfamily nmo

Function

nmo kinases, including Drosophila nemo, human NLK (nemo-like kinase), and C. elegans lit-1 are MAPK that modulate a wide variety of transcription factors in response to developmental and inflammatory signals. Unlike most other MAPKs, nmo kinases lack a tyrosine in their activation loop. Rather than being activated by MAP2Ks, they are directly activated by TAK1, a MAP3K from the MLK family. TAK1, in turn, is activated by signals from TGFb receptor kinases and inflammatory cytokines TNFa and IL1.

nmo is a largely nuclear protein, and known to phosphorylate many transcription factors, including STAT3, NFkB, Myb, SETDB1, Foxo1 and Mad, and is involved in a number of developmental programs, including Wnt and TGFb signaling. nmo signaling has been implicated in apoptosis and in ubiquitin-mediated degradation of target transcription factors, in both Drosophila, mammals. The C. elegans homolog, lit-1, is best known for its role in asymmetric cell division in the embryo, but is also known as a mediator of Wnt and Notch signaling.

Evolution

nmo kinases are found in single copy in all metazoan genomes, but not in other eukaryotes. nmo is named after the Drosophila member nemo; vertebrate homologs are named NLK (Nemo-Like Kinase).

Protein Structure

nmo kinases have a central kinase domain with non-domain extensions on either side, which may harbor transcription factor-interacting regions.