MAP4K2
Description
The MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2) is a protein-coding gene located on chromosome 11.
Mitogen-activated protein kinase kinase kinase kinase 2 is an enzyme that in humans is encoded by the MAP4K2 gene.
== Function == The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. A recent study showed that MAP4K2 is a direct kinase of LATS1/2 and thus regulates the Hippo pathway effectors YAP and TAZ.
== Interactions == MAP4K2 has been shown to interact with RAB8A and TRAF2.
MAP4K2 is a serine/threonine-protein kinase that plays a crucial role in the MAP kinase signal transduction pathway. It acts as a MAPK kinase kinase kinase (MAP4K) and primarily activates the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway, with a lesser effect on the p38 MAPKs signaling pathway. MAP4K2 is essential for efficient activation of JNKs in response to various stimuli, including pathogen-associated molecular patterns (PAMPs) like polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. It also contributes to JNK activation triggered by IL-1 and CD40 engagement, though to a lesser extent. MAP4K2's role in LPS signaling is particularly prominent, extending to the stimulation of c-Jun phosphorylation and the induction of IL-8. MAP4K2 enhances MAP3K1 oligomerization, potentially relieving N-terminal mediated MAP3K1 autoinhibition and leading to activation following autophosphorylation. It also activates the SAP/JNK and p38 MAPKs signaling pathways by activating the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. MAP4K2 may participate in regulating vesicle targeting or fusion.
MAP4K2 is also known as BL44, GCK, RAB8IP.
Associated Diseases
- multiple sclerosis
- Parkinson disease
- lysosomal storage disease
- Alzheimer disease
- osteoporosis-pseudoglioma syndrome
- Miyoshi myopathy
