Scientific Background: MAPKAPK3 is closely related to MAPKAPK2 sharing 72% nucleotide and 75% amino acid identity (1). MAPKAPK3 is activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of MAPKAPK3 as an integrative element of signaling in both mitogen and stress responses (2).
2. Ludwig, S. et al: 3pK, a novel mitogen-activated protein (MAP) kinase-activated protein kinase, is targeted by three MAP kinase pathways. Molec. Cell. Biol. 16: 6687-6697, 1996.
NCBI and Uniprot Product Information
NCBI Description
This gene encodes a member of the Ser/Thr protein kinase family. This kinase functions as a mitogen-activated protein kinase (MAP kinase)- activated protein kinase. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This kinase was shown to be activated by growth inducers and stress stimulation of cells. In vitro studies demonstrated that ERK, p38 MAP kinase and Jun N-terminal kinase were all able to phosphorylate and activate this kinase, which suggested the role of this kinase as an integrative element of signaling in both mitogen and stress responses. This kinase was reported to interact with, phosphorylate and repress the activity of E47, which is a basic helix-loop-helix transcription factor known to be involved in the regulation of tissue-specific gene expression and cell differentiation. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
Uniprot Description
Function: Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. Ref.1 Ref.7 Ref.8 Ref.11 Ref.12 Ref.14
Catalytic activity: ATP + a protein = ADP + a phosphoprotein. Ref.7
Enzyme regulation: Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors.
Subunit structure: Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface
By similarity. Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4. Ref.9 Ref.11
Subcellular location: Nucleus. Cytoplasm. Note: Predominantly located in the nucleus, when activated it translocates to the cytoplasm. Ref.10
Tissue specificity: Widely expressed, with a higher expression level observed in heart and skeletal muscle. No expression in brain. Ref.1 Ref.2
Post-translational modification: Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313
By similarity. Ref.1 Ref.2
Sequence similarities: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.Contains 1 protein kinase domain.
Research Articles on MAPKAPK3
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Product Notes
The MAPKAPK3 mapkapk3 (Catalog #AAA515410) is a Recombinant Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||E.coli!!Source Note||Recombinant full-length human MAPKAPK3 was expressed in E. coli cells. AAA Biotech's MAPKAPK3 can be used in a range of immunoassay formats including, but not limited to, Kinase Assay, Western Blot (WB). Researchers should empirically determine the suitability of the MAPKAPK3 mapkapk3 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "MAPKAPK3, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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