Disease relevance of MAPKAPK3

• 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region [1].
• Absence of mutations in the coding sequence of the potential tumor suppressor 3pK in metastatic melanoma [2].

High impact information on MAPKAPK3

• The other appeared to be MAPKAP kinase 3; however, it could not be excluded that also other p38-dependent kinases contributed [3].
• Here we show that 3pK is activated in vivo by the growth inducers serum and tetradecanoyl phorbol acetate in promyelocytic HL60 cells and transiently transfected embryonic kidney 293 cells [4].
• Activation or overexpression of 3pK resulted in phosphorylation of Bmi1 and other PcG members and their dissociation from chromatin [5].
• MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1 [5].
• E47 is a phosphoprotein, and we identified 3pK and MK2 as E47 kinases in vitro [6].

Biological context of MAPKAPK3

• Two candidate tumor suppressor genes from the human 3p21-p22 region MAPKAPK3 (3pK) and MLH1 were cloned into the episomal vector and transfected into engineered A9 and KRC/Y cells [7].
• In summary, the MAPK-activated protein kinases 3pK and MK2 were identified to form an assembly with the bHLH protein E47 suggesting that these kinases are regulators of E47 activity and E47-dependent gene expression [6].
• 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 substrate specificity [1].
• Transient transfection studies provided direct evidence that MAPKAPK-3 was capable of signaling to activate CREB transcriptional activity, as assessed by means of GAL4-CREB fusion protein construct coexpressed with GAL4-luciferase reporter construct [8].
• MAPKAP kinase-2 and MAPKAP kinase-3 were both activated in response to cellular stress, interleukin-1 and tumour necrosis factor in KB and HeLa cells, and with identical kinetics [9].

Anatomical context of MAPKAPK3

• Introduction of wild-type, but not kinase-dead mutant, MAPKAPK-3 cDNA, into a mouse ovarian cell line stimulated GAL4-CREB- dependent transcriptional activity approximately 3-fold [8].
• Anisomycin induced the phosphorylation of CapZIP at Ser-179 in Jurkat cells, which was prevented by SB 203580, consistent with phosphorylation by MAPKAP-K2 and/or MAPKAP-K3 [10].

Associations of MAPKAPK3 with chemical compounds

• 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 [6].
• A Noti-linking clone NL1-210 (D3S1656) that contains the human MAP kinase activated protein kinase (3PK) gene was localized to 3p21.2 on DAPI-banded and propidium iodide (R-bands)-stained chromosomes by fluorescence in situ hybridization (FISH) [11].

Regulatory relationships of MAPKAPK3

• 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 [12].

Other interactions of MAPKAPK3

• The activation status of p38 was correlated with the phosphorylation status of an upstream activator, MAPK kinase-3/6 and the expression of MAPK activated protein kinase-3, a downstream target [13].
• 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].
• In the preconditioned area, genes for MAPKAP kinase 3 and cathepsin G were up-regulated [14].

Analytical, diagnostic and therapeutic context of MAPKAPK3

• We identified 3pK as an interaction partner of PcG proteins, in vitro and in vivo, by yeast two-hybrid interaction and co-immunoprecipitation, respectively [5].

References