Dual specificity mitogen-activated protein kinase kinase 4

MAP2K4 is a dual specificity kinase that phosphorylates and activates the stress-activated protein kinase/c-Jun N-terminal kinases (JNK1/2/3) as an essential component of the SAP/JNK mitogen-activated protein kinase signal transduction pathway (UniProt: P45985). The protein also activates p38 MAPKs and plays a role in peripheral lymphoid homeostasis and mitochondrial apoptotic signaling through cytochrome c release.

MAP2K4 functions in stress response and immune regulation, with the JNK/p38 signaling cascade implicated in cellular stress adaptation and programmed cell death. No specific UniProt-annotated disease association is listed for this protein.

MAP2K4 is downregulated in Alzheimer's disease, with a mean log2 fold-change of −1.22 in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). This reduction may reflect diminished stress-response signaling capacity in the AD brain, potentially affecting cellular adaptation to pathogenic insults characteristic of neurodegeneration.