Mitogen-activated protein kinase kinase kinase 11 (MAP3K11)

Mitogen-activated protein kinase kinase kinase 11 (MAP3K11), also known as mixed lineage kinase 3 (MLK3), is a serine/threonine kinase and a member of the MAP kinase kinase kinase family[1][6]. It activates multiple MAP kinase pathways (JNK, p38, and ERK) by phosphorylating specific MAP2Ks, integrates upstream signals from small GTPases such as Rac1 and Cdc42, and plays a pivotal role in cellular processes including signal transduction, cell proliferation, apoptosis, and immune regulation[2][4][6]. MAP3K11 is implicated in cancer progression, neurodegenerative diseases (such as Parkinson's and Alzheimer's), and inflammation. It is considered a therapeutic target, with several small molecule inhibitors in preclinical or early clinical investigation[4].

Other names

Mixed lineage kinase 3MLK3PTK1SPRKMEKK11Src-homology 3 domain-containing proline-rich kinaseSH3 domain-containing proline-rich kinaseprotein-tyrosine kinase PTK1slipper (in Drosophila)

Inhibition of MAP3K11/MLK3 kinase activity reduces JNK pathway activation, leading to reduced cell survival, proliferation, migration, and neurodegeneration[4]. Blockade of MAP3K11 can potentiate pro-apoptotic signaling in cancer cells and is neuroprotective in models of neurodegeneration[4].