Interfering with MAP Kinase Docking Interactions: Implications and Perspectives for the p38 Route

Mayor, Federico; Jurado-Pueyo, María; Campos, Pedro M.; Murga, Cristina

doi:10.4161/cc.6.5.3920

Cited by 36 publications

(12 citation statements)

References 73 publications

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“…This is closely related to the conserved kinase interaction motif (KIM) found within MAPK phosphatases and comprises a cluster of positively charged amino acids, normally lysines or arginines, followed by a submotif containing two hydrophobic residues leucine, isoleucine, or valine separated by one residue ((K/R) 1–3 X 2–6 ϕ X ϕ) (5, 6). Swapping one D domain for another can completely change the specificity of protein-protein interactions, indicating that these motifs are essential to maintain binding selectivity among MAPK pathway components (7). A second type of docking motif named the DEF motif (for d ocking site for E RK F X F) has been found only in some subsets of MAPK substrates.…”

Section: Introductionmentioning

confidence: 99%

Distinct Docking Mechanisms Mediate Interactions between the Msg5 Phosphatase and Mating or Cell Integrity Mitogen-activated Protein Kinases (MAPKs) in Saccharomyces cerevisiae

Palacios

Dickinson

Sacristán-Reviriego

et al. 2011

Journal of Biological Chemistry

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Background: Dual specificity protein phosphatases (DSPs) bind MAPKs through specific interaction motifs.Results: A novel motif (IYT) in Msg5 mediates a common docking domain-independent interaction with the yeast cell integrity kinase Slt2.Conclusion: Distinct mechanisms allow Msg5 to differentially bind Slt2 and Mlp1 or mating/pseudohyphal MAPKs Fus3 and Kss1.Significance: Elucidation of the mechanisms by which MAPKs interact with key regulators is vital to understanding cell signaling.

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Section: Introductionmentioning

confidence: 99%

Distinct Docking Mechanisms Mediate Interactions between the Msg5 Phosphatase and Mating or Cell Integrity Mitogen-activated Protein Kinases (MAPKs) in Saccharomyces cerevisiae

Palacios

Dickinson

Sacristán-Reviriego

et al. 2011

Journal of Biological Chemistry

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“…9 Mammalian MAPK pathways mainly consist of three subfamilies: the p38 MAPK, the extracellular signal-related kinase (ERK), and the c-Jun N-terminal protein kinase (JNK). 10,11 Upon stimulation, MAPKs are activated through phosphorylation by upstream dual-specificity kinases. 12 Because the activation of JNK is believed to be important for cisplatin-induced cell death, modulation of JNK activity has an important impact on cisplatin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells

Wang

Zhou

Zhang³

et al. 2009

Cell Cycle

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Although cisplatin is a very effective anticancer agent against several types of cancer including ovarian cancer, the mechanisms of acquired resistance are not fully understood. By chronically exposing cisplatin to ovarian cancer cell lines, we established two cisplatin-resistant cell lines OV433 and tOV112D. Our results indicate that the mechanisms underlying their cisplatin resistance are distinct. In OV433 cells, cisplatin resistance is associated with increased expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1). By knocking down MKP-1 expression by siRNA or inhibiting MKP-1 expression by its pharmacological inhibitor triptolide, cisplatin-resistant OV433 cells became cisplatin-sensitive and subsequently increased cisplatin-induced apoptosis. In tOV112D cells, on the other hand, acquired cisplatin resistance is associated with increased levels of Bcl-2 protein. By inhibiting the activity of Bcl-2 protein with its pharmacological inhibitor gossypol or knocking down Bcl-2 expression by siRNA, cisplatin-resistant tOV112D cells became cisplatin-sensitive and subsequently increased cisplatin-induced apoptosis. therefore, our data suggest that the mechanisms of acquired cisplatin resistance vary among ovarian cancer cells, which involve upregulation of molecules associated with the cell survival pathways.

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“…These interactions collectively synchronize the activation and localization of p38 via feedback loops and crosstalk with other pathways [[41] and references therein]. Thus, a pool of excess, unactivated p38δ-WT could perturb this regulatory system, or may simply compete with the population of endogenous activated p38, resulting in inhibition of L1.…”

Section: Resultsmentioning

confidence: 99%

Deciphering fact from artifact when using reporter assays to investigate the roles of host factors on L1 retrotransposition

Cook

Tabor

2016

Mobile DNA

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BackgroundThe Long INterspersed Element-1 (L1, LINE-1) is the only autonomous mobile DNA element in humans and has generated as much as half of the genome. Due to increasing clinical interest in the roles of L1 in cancer, embryogenesis and neuronal development, it has become a priority to understand L1-host interactions and identify host factors required for its activity. Apropos to this, we recently reported that L1 retrotransposition in HeLa cells requires phosphorylation of the L1 protein ORF1p at motifs targeted by host cell proline-directed protein kinases (PDPKs), which include the family of mitogen-activated protein kinases (MAPKs). Using two engineered L1 reporter assays, we continued our investigation into the roles of MAPKs in L1 activity.ResultsWe found that the MAPK p38δ phosphorylated ORF1p on three of its four PDPK motifs required for L1 activity. In addition, we found that a constitutively active p38δ mutant appeared to promote L1 retrotransposition in HeLa cells. However, despite the consistency of these findings with our earlier work, we identified some technical concerns regarding the experimental methodology. Specifically, we found that exogenous expression of p38δ appeared to affect at least one heterologous promoter in an engineered L1 reporter, as well as generate opposing effects on two different reporters. We also show that two commercially available non-targeting control (NTC) siRNAs elicit drastically different effects on the apparent retrotransposition reported by both L1 assays, which raises concerns about the use of NTCs as normalizing controls.ConclusionsEngineered L1 reporter assays have been invaluable for determining the functions and critical residues of L1 open reading frames, as well as elucidating many aspects of L1 replication. However, our results suggest that caution is required when interpreting data obtained from L1 reporters used in conjunction with exogenous gene expression or siRNA.

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Interfering with MAP Kinase Docking Interactions: Implications and Perspectives for the p38 Route

Cited by 36 publications

References 73 publications

Distinct Docking Mechanisms Mediate Interactions between the Msg5 Phosphatase and Mating or Cell Integrity Mitogen-activated Protein Kinases (MAPKs) in Saccharomyces cerevisiae

Distinct Docking Mechanisms Mediate Interactions between the Msg5 Phosphatase and Mating or Cell Integrity Mitogen-activated Protein Kinases (MAPKs) in Saccharomyces cerevisiae

Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells

Deciphering fact from artifact when using reporter assays to investigate the roles of host factors on L1 retrotransposition

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