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Int J Mol Sci. 2019 Apr 27;20(9). pii: E2086. doi: 10.3390/ijms20092086.

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

Author information

1
Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491 Trondheim, Norway. yashwanth.subbannayya@ntnu.no.
2
Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore 575018, India. yashwanth.subbannayya@ntnu.no.
3
Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491 Trondheim, Norway. sneha.pinto@ntnu.no.
4
Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore 575018, India. sneha.pinto@ntnu.no.
5
Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491 Trondheim, Norway. korbinian.bosl@ntnu.no.
6
Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore 575018, India. keshav@yenepoya.edu.in.
7
Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491 Trondheim, Norway. richard.k.kandasamy@ntnu.no.
8
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0349 Oslo, Norway. richard.k.kandasamy@ntnu.no.

Abstract

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.

KEYWORDS:

TLR signaling; hematopoietic cells; integrated omics analysis

PMID:
31035605
PMCID:
PMC6539644
DOI:
10.3390/ijms20092086
[Indexed for MEDLINE]
Free PMC Article

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