MAP2K4(mitogen-activated protein kinase kinase 4), which is located on chromosome 17p11.2, with 399-ami- no acid protein (about 45 kDa), belongs to the family of protein kinases located upstream of the MAP kinases and responsible for their activation has been identified. MEK-4 (also called MEK4/MKK4) activates both p38 and JNK MAP kinases. MKK4 is a central mediator in the stress activated protein kinase signaling pathway that responds to a number of cellular and environmental stressors. By phosphorylating MAP kinases such as JNK, MKK4 can ultimately transmit stress signals to nuclear transcription factors that mediate various processes including prolifera- tion, apoptosis, and differentiation. Its distinct biological functions have been identified for MKK4 including a role in development, hepatogenesis, and metastasis suppres- sion.