Mitogen-activated protein kinase kinase kinase 10 (MLK2) (MLK2)

Mitogen-activated protein kinase kinase kinase 10 (MLK2) is a serine/threonine kinase belonging to the mixed lineage kinase family, characterized by its ability to activate the c-Jun N-terminal kinase (JNK) signaling pathway. It functions as a MAP kinase kinase kinase (MAP3K) by phosphorylating and activating downstream kinases such as MKK4 and MKK7 in response to various cellular stresses. Beyond its role in signal transduction, MLK2 is involved in vesicle trafficking through interactions with clathrin and dynamin, and it contributes to the regulation of microtubule dynamics. In disease, MLK2 has been implicated in neurodegenerative conditions like Parkinson's disease, where it is found in Lewy bodies and may mediate neuronal apoptosis. It also plays a role in oncology, where its overexpression is linked to increased cell proliferation and resistance to chemotherapy in cancers such as pancreatic ductal adenocarcinoma. Therapeutic targeting of MLK2 has primarily focused on small molecule inhibitors like CEP-1347, which aim to mitigate JNK-driven cell death, although achieving high selectivity remains a significant challenge in drug development.

Other names

MAP3K10Mixed lineage kinase 2MSTMEKK10Protein kinase MSTMKN28 kinase

Inhibition of kinase activity, specifically blocking the phosphorylation of MKK4 and MKK7 to prevent activation of the JNK signaling pathway.