Gene Symbol: MAPKAPK3
Description: mitogen-activated protein kinase-activated protein kinase 3
Alias: 3PK, MAPKAP-K3, MAPKAP3, MAPKAPK-3, MDPT3, MK-3, MAP kinase-activated protein kinase 3, MAPK-activated protein kinase 3, MAPKAP kinase 3, chromosome 3p kinase
Species: human
Products:     MAPKAPK3

Top Publications

  1. Zakowski V, Keramas G, Kilian K, Rapp U, Ludwig S. Mitogen-activated 3p kinase is active in the nucleus. Exp Cell Res. 2004;299:101-9 pubmed
    The MAPK-activated kinase 3pK (chromosome 3p kinase), also known as MAPKAPK-3, is a member of a family of kinases that are activated by more than one mitogen-activated protein kinase (MAPK)...
  2. Köther K, Nordhoff C, Masemann D, Varga G, Bream J, Gaestel M, et al. MAPKAP kinase 3 suppresses Ifng gene expression and attenuates NK cell cytotoxicity and Th1 CD4 T-cell development upon influenza A virus infection. FASEB J. 2014;28:4235-46 pubmed publisher
    ..Köther, K., Nordhoff, C., Masemann, D., Varga, G., Bream, J. H., Gaestel, M., Wixler, V., Ludwig, S. MAPKAP kinase 3 suppresses Ifng gene expression and attenuates NK cell cytotoxicity and Th1 CD4 T-cell development upon ..
  3. Reynoird N, Mazur P, Stellfeld T, Flores N, Lofgren S, Carlson S, et al. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. Genes Dev. 2016;30:772-85 pubmed publisher
    ..We further identified the stress response kinase MAPKAPK3 (MK3) as a new physiologic substrate of SMYD2 in PDAC cells...
  4. Meunier I, Lenaers G, Bocquet B, Baudoin C, Piro Megy C, Cubizolle A, et al. A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes a new retinal dystrophy involving Bruch's membrane and retinal pigment epithelium. Hum Mol Genet. 2016;25:916-26 pubmed publisher
    ..Whole-exome sequencing identified a heterozygous c.518T>C (p.Leu173Pro) mutation in MAPKAPK3 that segregates with the disease in 14 affected and 28 unaffected siblings from three generations...
  5. Shiryaev A, Dumitriu G, Moens U. Distinct roles of MK2 and MK5 in cAMP/PKA- and stress/p38MAPK-induced heat shock protein 27 phosphorylation. J Mol Signal. 2011;6:4 pubmed publisher
    ..Thus, despite the same substrate specificity towards HSP27, MK2 and MK5 are implicated in different signaling pathways causing actin reorganization. ..
  6. Prickaerts P, Niessen H, Dahlmans V, Spaapen F, Salvaing J, Vanhove J, et al. MK3 modulation affects BMI1-dependent and independent cell cycle check-points. PLoS ONE. 2015;10:e0118840 pubmed publisher
  7. Voncken J, Niessen H, Neufeld B, Rennefahrt U, Dahlmans V, Kubben N, et al. MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1. J Biol Chem. 2005;280:5178-87 pubmed
    ..Here we present the novel finding that the PcG protein Bmi1 is phosphorylated by 3pK (MAPKAP kinase 3), a convergence point downstream of activated ERK and p38 signaling pathways and implicated in ..
  8. Ngo H, Pham L, Kim J, Lim Y, Hwang S. Modulation of mitogen-activated protein kinase-activated protein kinase 3 by hepatitis C virus core protein. J Virol. 2013;87:5718-31 pubmed publisher
    ..Of these candidates, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) was selected for further characterization...
  9. Jean Charles A, Merle H, Audo I, Desoudin C, Bocquet B, Baudoin C, et al. Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights. Ophthalmology. 2016;123:2196-204 pubmed publisher
    ..of the knowledge of its associated mutated gene mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3), an actor in the p38 mitogen-activated protein kinase pathway. Clinical and molecular study...

More Information


  1. Zhou T, Liang B, Su G, Gong W, Li H, Tian L, et al. Identification of ubiquitin target proteins using cell-based arrays. J Proteome Res. 2007;6:4397-406 pubmed
    ..More importantly, 24 of those 40 proteins, such as MAPKAPK3, NLK, and RhoGDI2, are previously not known as the targets of ubiquitin...
  2. Lavoie J, Lambert H, Hickey E, Weber L, Landry J. Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol. 1995;15:505-16 pubmed
    ..The level of protection provided by HSP27 during heat shock may thus represent the contribution of better maintenance of actin filament integrity to overall cell survival. ..
  3. Knebel A, Haydon C, Morrice N, Cohen P. Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and -insensitive pathways. Biochem J. 2002;367:525-32 pubmed
    ..Since the phosphorylation of Ser-377 does not inhibit eEF2 kinase in vitro, our results suggest that anisomycin or TNF-alpha inhibit eEF2 kinase via the phosphorylation of Ser-359. ..
  4. Mayo L, Kessler K, Pincheira R, Warren R, Donner D. Vascular endothelial cell growth factor activates CRE-binding protein by signaling through the KDR receptor tyrosine kinase. J Biol Chem. 2001;276:25184-9 pubmed
    ..Thus, KDR/Flk1 uses multiple pathways to transmit signals into the nucleus where CREB becomes activated. These results suggest that CREB may play a role in alterations of gene expression important to angiogenesis. ..
  5. Neufeld B, Grosse Wilde A, Hoffmeyer A, Jordan B, Chen P, Dinev D, et al. Serine/Threonine kinases 3pK and MAPK-activated protein kinase 2 interact with the basic helix-loop-helix transcription factor E47 and repress its transcriptional activity. J Biol Chem. 2000;275:20239-42 pubmed
    ..we identified the basic helix-loop-helix (bHLH) transcription factor E47 as an interaction partner of chromosome 3p kinase (3pK) and MAPKAP-K2 (MK2)...
  6. Joneson T, Bar Sagi D. Ras effectors and their role in mitogenesis and oncogenesis. J Mol Med (Berl). 1997;75:587-93 pubmed
    ..The relative contribution of the different Ras effector pathways to the mitogenic and oncogenic effects of Ras are discussed. ..
  7. Kumar S, McDonnell P, Gum R, Hand A, Lee J, Young P. Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochem Biophys Res Commun. 1997;235:533-8 pubmed
    ..These data suggest that SAPK3 and SAPK4 form a distinct subset of the p38 MAP kinases with different expression pattern, response to stimuli, substrate specificity, and inhibitor sensitivity. ..
  8. Clifton A, Young P, Cohen P. A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress. FEBS Lett. 1996;392:209-14 pubmed
    ..These results establish that MAPKAP kinase-3 lies 'downstream' of SAPK-2 and that it is likely to have overlapping or identical substrates to MAPKAP kinase-2 in vivo. ..
  9. Wei Y, An Z, Zou Z, Sumpter R, Su M, Zang X, et al. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. elife. 2015;4: pubmed publisher
    ..kinases, members of the p38 mitogen-activated protein kinase (MAPK) signaling pathway MAPKAPK2 (MK2) and MAPKAPK3 (MK3), positively regulate starvation-induced autophagy by phosphorylating an essential ATG protein, Beclin 1, at ..
  10. Vogl T, Ludwig S, Goebeler M, Strey A, Thorey I, Reichelt R, et al. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood. 2004;104:4260-8 pubmed
    ..Thus, the complex of MRP8/MRP14 is the first characterized molecular target integrating MAPK- and calcium-dependent signals during migration of phagocytes. ..
  11. Luig C, Köther K, Dudek S, Gaestel M, Hiscott J, Wixler V, et al. MAP kinase-activated protein kinases 2 and 3 are required for influenza A virus propagation and act via inhibition of PKR. FASEB J. 2010;24:4068-77 pubmed publisher
    ..Accordingly, knockdown of MKs resulted in enhanced phosphorylation of PKR and its substrate eIF2?. ..
  12. Simkhovich B, Abdishoo S, Poizat C, Hale S, Kedes L, Kloner R. Gene activity changes in ischemically preconditioned rabbit heart gene: discovery array study. Heart Dis. 2002;4:63-9 pubmed
    ..In the preconditioned area, genes for MAPKAP kinase 3 and cathepsin G were up-regulated...
  13. Tanoue T, Maeda R, Adachi M, Nishida E. Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions. EMBO J. 2001;20:466-79 pubmed
    ..amino acids in this site of ERK2 for corresponding residues of p38 converted the docking specificity for MAPKAPK-3/3pk, which is a dominant target of p38, from the ERK2 type to the p38 type, and vice versa...
  14. Eyers C, McNeill H, Knebel A, Morrice N, Arthur S, Cuenda A, et al. The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ. Biochem J. 2005;389:127-35 pubmed
    ..Osmotic shock or anisomycin triggered the dissociation of CapZIP from CapZ in Jurkat cells, suggesting that phosphorylation of CapZIP may regulate the ability of CapZ to remodel actin filament assembly in vivo. ..
  15. Sithanandam G, Latif F, Duh F, Bernal R, Smola U, Li H, et al. 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. Mol Cell Biol. 1996;16:868-76 pubmed
    ..Here we demonstrate that the new gene, referred to as 3pK (for chromosome 3p kinase), in fact encodes a mitogen-activated protein kinase-regulated protein serine-threonine kinase with a novel ..
  16. Ludwig S, Engel K, Hoffmeyer A, Sithanandam G, Neufeld B, Palm D, et al. 3pK, a novel mitogen-activated protein (MAP) kinase-activated protein kinase, is targeted by three MAP kinase pathways. Mol Cell Biol. 1996;16:6687-97 pubmed
    Recently we have identified a mitogen-activated protein kinase (MAPK)-activated protein kinase, named 3pK (G. Sithanandam, F. Latif, U. Smola, R. A. Bernal, F.-M. Duh, H. Li, I. Kuzmin, V. Wixler, L. Geil, S. Shresta, P. A. Lloyd, S...
  17. Cheng R, Felicetti B, Palan S, Toogood Johnson I, Scheich C, Barker J, et al. High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand. Protein Sci. 2010;19:168-73 pubmed publisher
  18. Tsukada H, Ochi H, Maekawa T, Abe H, Fujimoto Y, Tsuge M, et al. A polymorphism in MAPKAPK3 affects response to interferon therapy for chronic hepatitis C. Gastroenterology. 2009;136:1796-805.e6 pubmed publisher
    ..A/T] and rs616589 [G/A]), located in intron 2 of mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) that were associated with the outcome of IFN therapy in patients infected with hepatitis C virus (HCV) genotype ..
  19. Nakanishi K, Saito Y, Azuma N, Sasajima T. Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia. J Vasc Surg. 2013;57:182-93, 193.e1-10 pubmed publisher
    ..two previously unrecognized IH-related genes, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) and four-and-a-half LIM domains 5 (FHL5)...
  20. Ben Levy R, Leighton I, Doza Y, Attwood P, Morrice N, Marshall C, et al. Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2. EMBO J. 1995;14:5920-30 pubmed
    ..The mutant Asp222/Asp334 was 20% as active as phosphorylated MAPKAP kinase-2, and this constitutively active form may be useful for studying its physiological roles. ..
  21. McLaughlin M, Kumar S, McDonnell P, Van Horn S, Lee J, Livi G, et al. Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase. J Biol Chem. 1996;271:8488-92 pubmed
    ..These data suggest that MAPKAP kinase-3 is activated by stress and cytokines and is a novel substrate of CSBP both in vitro and in vivo. ..
  22. Wei M, Latif F, Bader S, Kashuba V, Chen J, Duh F, et al. Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG. Cancer Res. 1996;56:1487-92 pubmed
    ..This large cosmid clone contig and high resolution maps will prove crucial in the identification of the lung cancer TSG(s). ..