MAP2K2

MAP2K2, also known as MEK2, is a dual-specificity serine/threonine protein kinase that plays a central role in the mitogen-activated protein kinase (MAPK) signaling cascade, particularly the MAPK/ERK pathway. The MAP2K2-encoded kinase acts downstream of RAF kinases and upstream of ERK1/2, phosphorylating these effector kinases to promote their activation and subsequent translocation to the nucleus where they regulate transcription factors and cell-cycle regulators.

In the MAPK/ERK pathway, MAP2K2 is activated by upstream kinases in response to growth factors and other mitogenic stimuli. Once activated, MEK2 phosphorylates ERK1/2 on their activation motifs, enabling ERK signaling to control processes such as cell proliferation, differentiation, and survival. MEK1 and MEK2 have overlapping roles but can also have distinct contributions in different cell types and developmental contexts. The proteins are predominantly cytosolic but can shuttle to the nucleus upon activation and commonly interact with scaffolding proteins that coordinate signaling specificity.

MAP2K2 is widely expressed across tissues and often functions redundantly with MAP2K1 (MEK1). Dysregulation of MEK2 signaling has been implicated in various cancers and other disorders, where constitutive ERK activation promotes oncogenic processes. Pharmacological inhibitors that target MEK1/2, such as trametinib and cobimetinib, are used in targeted cancer therapies, reflecting the clinical relevance of MAP2K2 in disease.