Редактирование: MAPKAPK2

MAP kinase-activated protein kinase 2 (EC 2.7.11.1) (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2)

==Publications==

{{medline-entry
|title=Quantitative In Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31801093
|abstract=Metformin is the front-line treatment for type 2 diabetes worldwide. It acts via effects on glucose and lipid metabolism in metabolic tissues, leading to enhanced insulin sensitivity. Despite significant effort, the molecular basis for metformin response remains poorly understood, with a limited number of specific biochemical pathways studied to date. To broaden our understanding of hepatic metformin response, we combine phospho-protein enrichment in tissue from genetically engineered mice with a quantitative proteomics platform to enable the discovery and quantification of basophilic kinase substrates in vivo. We define proteins whose binding to 14-3-3 are acutely regulated by metformin treatment and/or loss of the serine/threonine kinase, LKB1. Inducible binding of 250 proteins following metformin treatment is observed, 44% of which proteins bind in a manner requiring LKB1. Beyond AMPK, metformin activates protein kinase D and [[MAPKAPK2]] in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response. Deeper analysis uncovered substrates of AMPK in endocytosis and calcium homeostasis.
|mesh-terms=* AMP-Activated Protein Kinases
* Animals
* Calcium
* Cell Line
* Endocytosis
* HEK293 Cells
* Homeostasis
* Humans
* Intracellular Signaling Peptides and Proteins
* Liver
* Metformin
* Mice
* Phosphorylation
* Protein Kinase C
* Protein-Serine-Threonine Kinases
* Proteomics
* Signal Transduction
|keywords=* AMPK3
* LKB1
* PKD1
* STIM1
* aging
* calcium
* diabetes
* kinases
* liver
* metformin
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980792
}}
{{medline-entry
|title=Cell fate regulation by reticulon-4 in human prostate cancers.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30480803
|abstract=Reticulon-4 ([[RTN4]]), a reticulon family protein localized in the endoplasmic reticulum, is reported to be involved in multiple physiological processes like neuroendocrine secretion and membrane trafficking in neuroendocrine cells. Previous studies have presented a great potential of [[RTN4]] for the treatment of autoimmune-mediated demyelinating diseases and spinal cord injury regeneration. While interaction with Bcl-2 and Bcl-2-like family in apoptosis modulation implicated its possible role in various human cancers. However, the investigation of this gene in prostate cancer is mainly ignored. Here in our current study, we focused on its role in prostate cancer and found that [[RTN4]] DNA copy numbers were higher in prostate cancer than normal prostate gland while its RNA and protein expressions were relatively lower. Chromosomal neighbor gene [[EML6]] had similar expression patterns with [[RTN4]] in prostate cancer tissues and cell lines, and further research found that they could be both targeted by miR-148a-3p. Lentivirus-mediated [[RTN4]] overexpression potently inhibited DU145 and LNCaP cells proliferation. Cell cycle was blocked in G2/M phase and significant cell senescence was observed in [[RTN4]] overexpressed prostate cancer cells. Finally, interaction networks in the normal prostate gland and cancer tissues further revealed that [[RTN4]] maybe phosphorylated by [[MAPKAPK2]] and [[FYN]] at tyrosine 591 and serine 107, respectively. All these results implied that [[RTN4]] might somehow participate in prostate tumor progression, and this elicits possibility to develop or identify selective agents targeting [[RTN4]] for prostate cancer therapy.
|mesh-terms=* Apoptosis
* Cell Cycle
* Cell Line
* Cell Line, Tumor
* Cell Proliferation
* Endoplasmic Reticulum
* Gene Expression Regulation, Neoplastic
* HEK293 Cells
* Humans
* Intracellular Signaling Peptides and Proteins
* Male
* MicroRNAs
* Nogo Proteins
* PC-3 Cells
* Phosphorylation
* Prostatic Neoplasms
* Protein-Serine-Threonine Kinases
* Proteomics
* Proto-Oncogene Proteins c-bcl-2
|keywords=* cell proliferation
* cell senescence
* miR-148a-3p
* prostate cancer
* reticulon-4
|full-text-url=https://sci-hub.do/10.1002/jcp.27704
}}
{{medline-entry
|title=Rapamycin and the inhibition of the secretory phenotype.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28167236
|abstract=Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Cell senescence is a complex process that can be triggered by multiple challenges. Recently it has been observed that the composition of the secretory phenotype or SASP depends on the insult that triggers cell senescence. Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while silencing the Nrf2 gene induces premature senescence. We have found that rapamycin activates the Nrf2 pathway to regulate cell cycle arrest, but not the production of SASP, which is regulated by a different pathway, probably involving the inhibition of [[MAPKAPK2]].
|mesh-terms=* Animals
* Cell Cycle Checkpoints
* Cellular Senescence
* Fibroblasts
* Humans
* NF-E2-Related Factor 2
* Phenotype
* Protein Kinase Inhibitors
* Signal Transduction
* Sirolimus
* TOR Serine-Threonine Kinases
|keywords=* Cell cycle arrest
* Cell senescence
* Nrf2
* Rapamycin
* SASP
|full-text-url=https://sci-hub.do/10.1016/j.exger.2017.01.026
}}
{{medline-entry
|title=Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26046488
|abstract=Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different [[MAPKAPK2]] (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells. 

|keywords=* MK2 inhibitor
* Suzuki-Miyaura
* Werner syndrome
* boronic acid
* cell aging
* cross-coupling
* heterocycles
* microwave-assisted synthesis
* pyrazoles
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491660
}}