MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells

Schwermann, Jessica; Rathinam, Chozhavendan; Schubert, Maria; Schumacher, Stefanie; Noyan, Fatih; Koseki, Haruhiko; Kotlyarov, Alexey; Klein, Christoph; Gaestel, Matthias

doi:10.1038/emboj.2009.100

Cited by 28 publications

(23 citation statements)

References 61 publications

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“…Following stress stimulation, MK2/3 phosphorylate components of the complex, such as BMI1, a protein involved in the selfrenewal of hematopoietic stem cells. Interestingly, a recent study demonstrated that hematopoietic stem cells in MK2-deficient mice are reduced in number and show an impaired ability for competitive repopulation in vivo (320).…”

Section: Mk2/3mentioning

confidence: 99%

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Cargnello

Roux

2011

Microbiol Mol Biol Rev

2,529

1,619

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SUMMARY The mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs by relaying extracellular signals to intracellular responses. In mammals, there are more than a dozen MAPK enzymes that coordinately regulate cell proliferation, differentiation, motility, and survival. The best known are the conventional MAPKs, which include the extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino-terminal kinases 1 to 3 (JNK1 to -3), p38 (α, β, γ, and δ), and ERK5 families. There are additional, atypical MAPK enzymes, including ERK3/4, ERK7/8, and Nemo-like kinase (NLK), which have distinct regulation and functions. Together, the MAPKs regulate a large number of substrates, including members of a family of protein Ser/Thr kinases termed MAPK-activated protein kinases (MAPKAPKs). The MAPKAPKs are related enzymes that respond to extracellular stimulation through direct MAPK-dependent activation loop phosphorylation and kinase activation. There are five MAPKAPK subfamilies: the p90 ribosomal S6 kinase (RSK), the mitogen- and stress-activated kinase (MSK), the MAPK-interacting kinase (MNK), the MAPK-activated protein kinase 2/3 (MK2/3), and MK5 (also known as p38-regulated/activated protein kinase [PRAK]). These enzymes have diverse biological functions, including regulation of nucleosome and gene expression, mRNA stability and translation, and cell proliferation and survival. Here we review the mechanisms of MAPKAPK activation by the different MAPKs and discuss their physiological roles based on established substrates and recent discoveries.

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Section: Mk2/3mentioning

confidence: 99%

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Cargnello

Roux

2011

Microbiol Mol Biol Rev

2,529

1,619

View full text Add to dashboard Cite

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“…Notably, PcG factors have been reported to be linked with RA, FGFs, SHH and MAP kinase pathways (Schwermann et al, 2009;Shi et al, 2014;van der Velden et al, 2012;Wu et al, 2013;Yokobayashi et al, 2013). By such interactions with signaling pathways, PcG factors may contribute to the compartmentalization of outgrowing or enlarging fetal tissues by regulating the expression of developmental genes.…”

Section: Discussionmentioning

confidence: 99%

RING1 contributes to early proximal-distal specification of the forelimb bud by restricting Meis2 expression

et al. 2015

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Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry.

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“…But not only the composition of the complex is decisive. PRC1 is also regulated by external MAKPK kinases such as Mapkap2 (MK2) to improve the balancing between HSC self-renewal and differentiation [45].…”

Section: Resultsmentioning

confidence: 99%

HSC-Explorer: A Curated Database for Hematopoietic Stem Cells

et al. 2013

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HSC-Explorer (http://mips.helmholtz-muenchen.de/HSC/) is a publicly available, integrative database containing detailed information about the early steps of hematopoiesis. The resource aims at providing fast and easy access to relevant information, in particular to the complex network of interacting cell types and molecules, from the wealth of publications in the field through visualization interfaces. It provides structured information on more than 7000 experimentally validated interactions between molecules, bioprocesses and environmental factors. Information is manually derived by critical reading of the scientific literature from expert annotators. Hematopoiesis-relevant interactions are accompanied with context information such as model organisms and experimental methods for enabling assessment of reliability and relevance of experimental results. Usage of established vocabularies facilitates downstream bioinformatics applications and to convert the results into complex networks. Several predefined datasets (Selected topics) offer insights into stem cell behavior, the stem cell niche and signaling processes supporting hematopoietic stem cell maintenance. HSC-Explorer provides a versatile web-based resource for scientists entering the field of hematopoiesis enabling users to inspect the associated biological processes through interactive graphical presentation.

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MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells

Cited by 28 publications

References 61 publications

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

RING1 contributes to early proximal-distal specification of the forelimb bud by restricting Meis2 expression

HSC-Explorer: A Curated Database for Hematopoietic Stem Cells

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