Mitogen-activated protein kinase kinase kinase 10 (MAP3K10)

Mitogen-activated protein kinase kinase kinase 10 (MAP3K10, also known as MLK2 or MEKK10) is a serine/threonine protein kinase in the MAP kinase signaling cascade, primarily activating the JNK (c-Jun N-terminal kinase) and MKK4/SEK1 pathways[2][5]. It functions in diverse cellular processes including apoptosis (notably in neurons), cell proliferation, and inflammatory response regulation[1][2][4]. MAP3K10 is directly regulated by microRNAs (e.g., miR-126 in vascular pathologies), and is involved in signaling downstream of nerve growth factor and transforming growth factor-beta (TGF-β)[1][2][4]. Dysregulation of MAP3K10 is linked to cardiovascular disease, certain cancers (especially pancreatic ductal adenocarcinoma, where it promotes proliferation and chemoresistance), and neurodegeneration[1][4][7]. Its structure includes SH3 and leucine zipper domains facilitating protein interactions[3][7]. MAP3K10 is expressed in various tissues but highly in brain and skeletal muscle[5][6]. As a regulator of major signaling cascades, it is considered a promising therapeutic target; however, specificity is required due to the broad physiological roles of the kinase family. Supporting literature and results confirm this target is well-characterized and therapeutically relevant[1][2][4][5].

Other names

MLK2MEKK10Mixed lineage kinase 2Protein kinase MSTMST

Inhibition of MAP3K10 reduces activation of the JNK signaling pathway, thereby modulating apoptosis, proliferation, and inflammatory responses[1]. Blocking kinase activity suppresses downstream signaling cascades (JNK and p38 MAPK)[2][4]. May reduce nerve growth factor-induced neuronal apoptosis or improve chemosensitivity in cancer[1].