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GCK Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with RAB8A. Highly expressed in germinal center but not mantle zone B-cells. Also expressed in lung, brain and placenta and at lower levels in other tissues examined. The tumor necrosis factor (TNF), as well as endotoxins and proinflammatory stimuli such as polyinosine- polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Note: This description may include information from UniProtKB.
Protein type: EC; KHS subfamily; Kinase, protein; Motility/polarity/chemotaxis; Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); STE group; STE20 family
Chromosomal Location of Human Ortholog: 11q13.1
Cellular Component: cytoplasm
Molecular Function: ATP binding; MAP kinase kinase kinase kinase activity; mitogen-activated protein kinase kinase kinase binding; protein binding; protein serine/threonine kinase activity
Biological Process: activation of JNK activity; immune response; JNK cascade; positive regulation of JNK cascade; protein amino acid phosphorylation; regulation of apoptosis; regulation of mitotic cell cycle
Reference #:  Q12851 (UniProtKB)
Alt. Names/Synonyms: B lymphocyte serine/threonine protein kinase; B lymphocyte serine/threonine-protein kinase; BL44; GC kinase; GCK; Germinal center kinase; germinal centre kinase (GC kinase); M4K2; MAP4K2; MAPK/ERK kinase kinase kinase 2; MEK kinase kinase 2; MEKKK 2; Mitogen-activated protein kinase kinase kinase kinase 2; Rab8 interacting protein; Rab8-interacting protein; RAB8IP
Gene Symbols: MAP4K2
Molecular weight: 91,556 Da
Basal Isoelectric point: 5.91  Predict pI for various phosphorylation states
CST Pathways:  SAPK/JNK Signaling Cascades
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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