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 2.7.11.1; 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: 19|19 A
Cellular Component:  cytoplasm; Golgi apparatus; membrane; plasma membrane
Molecular Function:  ATP binding; kinase activity; MAP kinase kinase kinase kinase activity; mitogen-activated protein kinase kinase kinase binding; nucleotide binding; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process:  activation of JUN kinase activity; activation of protein kinase activity; immune system process; innate immune response; intracellular signal transduction; phosphorylation; positive regulation of JNK cascade; protein phosphorylation; signal transduction by protein phosphorylation; stress-activated protein kinase signaling cascade; vesicle targeting
Reference #:  Q61161 (UniProtKB)
Alt. Names/Synonyms: AI385662; BL44; GCK; Germinal center kinase; M4K2; Map4k2; MAPK/ERK kinase kinase kinase 2; MEK kinase kinase 2; MEKKK 2; MGC143893; MGC143894; mitogen activated protein kinase kinase kinase kinase 2; Mitogen-activated protein kinase kinase kinase kinase 2; OTTMUSP00000020164; RAB8 interacting protein; Rab8-interacting protein; Rab8ip
Gene Symbols: Map4k2
Molecular weight: 91,265 Da
Basal Isoelectric point: 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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GCK

Protein Structure Not Found.

Cross-references to other databases:  STRING  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene