SAPK/Erk kinase (SEK1), also known as MKK4 or Jun kinase kinase (JNKK), activates the MAP kinase homologues SAPK and JNK in response to various cellular stresses and inflammatory cytokines. Activation of SEK1 occurs throμgh phosphorylation of serine and threonine residues at positions 257 and 261, respectively, by MEKK. Like MEK, SEK is a dual-specificity protein kinase that phosphorylates SAPK/JNK at a conserved T*PY* site in its activation loop. Phosphorylation by Akt at Ser80 inhibits SEK1 and suppresses the stress-activated signal transduction.