scholarly journals The Dual Specificity Phosphatases M3/6 and MKP-3 Are Highly Selective for Inactivation of Distinct Mitogen-activated Protein Kinases

1996 ◽  
Vol 271 (44) ◽  
pp. 27205-27208 ◽  
Author(s):  
Marco Muda ◽  
Aspasia Theodosiou ◽  
Nanda Rodrigues ◽  
Ursula Boschert ◽  
Montserrat Camps ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Mitogen Activated Protein Kinases ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

scholarly journals Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability

2019 ◽  
Vol 20 (11) ◽  
pp. 2668 ◽  
Author(s):  
Hsueh-Fen Chen ◽  
Huai-Chia Chuang ◽  
Tse-Hua Tan
Keyword(s):  
Signal Transduction ◽  
Protein Stability ◽  
Protein Kinases ◽  
Post Translational Modifications ◽  
Mitogen Activated Protein Kinases ◽  
Cell Responses ◽  
Dual Specificity ◽  
Duration Magnitude ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications.

scholarly journals Dynamics of Dual Specificity Phosphatases and Their Interplay with Protein Kinases in Immune Signaling

2019 ◽  
Vol 20 (9) ◽  
pp. 2086 ◽  
Author(s):  
Yashwanth Subbannayya ◽  
Sneha M. Pinto ◽  
Korbinian Bösl ◽  
T. S. Keshava Prasad ◽  
Richard K. Kandasamy
Keyword(s):  
Immune Response ◽  
Protein Kinases ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Tlr4 Signaling ◽  
Cyclin Dependent Kinases ◽  
Therapeutic Modalities ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

Dual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen-activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focus on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR, and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study have the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.

scholarly journals Dynamics of dual specificity phosphatases and their interplay with protein kinases in immune signaling

2019 ◽  
Author(s):  
Yashwanth Subbannayya ◽  
Sneha M. Pinto ◽  
Korbinian Bösl ◽  
T. S. Keshava Prasad ◽  
Richard K. Kandasamy
Keyword(s):  
Immune Response ◽  
Protein Kinases ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Tlr4 Signaling ◽  
Cyclin Dependent Kinases ◽  
Therapeutic Modalities ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

AbstractDual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focused on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSP-mediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study has the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.

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