MAP3K4

MAP3K4, also known as mitogen-activated protein kinase kinase kinase 4, is a serine/threonine kinase that functions as part of the MAPK signaling cascade. It is a member of the MAP kinase kinase kinase (MAP3K) family and is encoded by the MAP3K4 gene in humans.

MAP3K4 acts as an upstream activator of the JNK signaling module. It phosphorylates and activates the MAP kinase kinases MKK4 (MAP2K4) and MKK7 (MAP2K7), which in turn activate the c-Jun N-terminal kinases (JNKs). Depending on cellular context, MAP3K4 can also influence p38 MAPK signaling in response to stress or inflammatory cues, contributing to transcriptional programs related to stress response, apoptosis, and differentiation.

Regulation of MAP3K4 is controlled by cellular stress, cytokines, and developmental cues. Activation leads to changes in gene expression and cytoskeletal dynamics through downstream MAPK pathways. The protein contains a C-terminal kinase domain responsible for its catalytic activity and an N-terminal regulatory region that participates in signal integration.

MAP3K4 has been implicated in human disease and development. Genetic or functional alterations affecting MAP3K4 signaling have been studied in cancer and in developmental contexts, and model organisms with altered MAP3K4 function show defects consistent with disruptions in stress-activated signaling pathways. However, the precise contributions of MAP3K4 can be tissue- and context-dependent and are the subject of ongoing research.

MAP3K4 interacts with core components of the MAPK cascade, most notably the MAPKKs MKK4 and MKK7, to propagate signals to JNK-dependent transcriptional responses. Additional interactors and regulatory partners have been described in various cell types.