Mitogen-activated protein kinase kinase kinase 6 (MAP3K6)

Mitogen-activated protein kinase kinase kinase 6 (MAP3K6) is a serine/threonine protein kinase that functions as a component of MAP kinase signal transduction cascades. It is involved in transmitting signals from the cell surface to the nucleus, particularly through activation of the JNK pathway and, to a lesser extent, the p38 MAP kinase pathway, but not the ERK pathway. MAP3K6 plays a crucial role in regulating angiogenic signaling by modulating expression of vascular endothelial growth factor (VEGF), influencing endothelial cell proliferation and capillary formation, and thereby affecting tumor growth in vivo. Germline mutations in MAP3K6 have been implicated in familial cases of gastric cancer and may act as predisposing factors by compromising tumor suppressor functions, sometimes in conjunction with a second somatic hit. Although it interacts with other kinases such as MAP3K5/ASK1 and participates in apoptotic and stress signaling, no approved drugs are currently known to act directly on MAP3K6.

Other names

MEKK6ASK2MAPKKK6Apoptosis signal-regulating kinase 2

No drugs directly target MAP3K6; experimentally, inhibitors would interfere with kinase activity and downstream signal transduction, especially VEGF signaling and JNK pathway activation.