MLK3 (Mixed lineage kinase 3) is a serine/threonine kinase that has an amino-terminal SH3 domain followed by the kinase domain and two leucine zippers, a cdc42/Rac1 binding (CRIB) domain and several other domains/motifs at the carboxy-terminal region. MLK3 functions as a MAPKKK of the SAPK/JNK stress pathway by directly phosphorylating SEK1/MKK4 and MKK7, althoμgh it is controversial whether MLK3 is involved in p38 stress pathway activation. MLK3 also functions as an IkB kinase and mediates the activation of the transcriptional factor NF-kB stimulated by CD3/CD28, sμggesting a role for MLK3 in immune and inflammatory responses.