Quantitative phosphoproteomic analysis of IL-33-mediated signaling

Sneha M. Pinto, Raja Sekhar Nirujogi, Pamela Leal Rojas, Arun H. Patil, Srikanth S. Manda, Yashwanth Subbannayya, Juan Carlos Roa, Aditi Chatterjee, T. S.Keshava Prasad, Akhilesh Pandey

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines that plays diverse roles in the regulation of immune responses. IL-33 exerts its effects through a heterodimeric receptor complex resulting in the production and release of proinflammatory cytokines. A detailed understanding of the signaling pathways activated by IL-33 is still unclear. To gain insights into the IL-33-mediated signaling mechanisms, we carried out a SILAC-based global quantitative phosphoproteomic analysis that resulted in the identification of 7191 phosphorylation sites derived from 2746 proteins. We observed alterations in the level of phosphorylation in 1050 sites corresponding to 672 proteins upon IL-33 stimulation. We report, for the first time, phosphorylation of multiple protein kinases, including mitogen-activated protein kinase activated protein kinase 2 (Mapkapk2), receptor (TNFRSF) interacting serine-threonine kinase 1 (Ripk1), and NAD kinase (Nadk) that are induced by IL-33. In addition, we observed IL-33-induced phosphorylation of several protein phosphatases including protein tyrosine phosphatase, nonreceptor-type 12 (Ptpn12), and inositol polyphosphate-5-phosphatase D (Inpp5d), which have not been reported previously. Network analysis revealed an enrichment of actin binding and cytoskeleton reorganization that could be important in macrophage activation induced by IL-33. Our study is the first quantitative analysis of IL-33-regulated phosphoproteome. Our findings significantly expand the understanding of IL-33-mediated signaling events and have the potential to provide novel therapeutic targets pertaining to immune-related diseases such as asthma where dysregulation of IL-33 is observed. All MS data have been deposited in the ProteomeXchange with identifier PXD000984 (http://proteomecentral.proteomexchange.org/dataset/PXD000984).

Original languageEnglish (US)
Pages (from-to)532-544
Number of pages13
JournalProteomics
Volume15
Issue number2-3
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Chemical analysis
Phosphorylation
Receptor-Interacting Protein Serine-Threonine Kinase 2
Protein Kinases
Interleukin-33
Cytokines
Polyphosphates
Protein Tyrosine Phosphatases
Macrophage Activation
Macrophages
Phosphoprotein Phosphatases
Protein-Serine-Threonine Kinases
Immune System Diseases
Inositol
Electric network analysis
Mitogen-Activated Protein Kinases
Actin Cytoskeleton
Interleukin-1
Phosphoric Monoester Hydrolases
Actins

Keywords

  • Cell biology
  • Immune disorders
  • Immunoaffinity purification
  • Inflammation
  • RhoGTPases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Pinto, S. M., Nirujogi, R. S., Rojas, P. L., Patil, A. H., Manda, S. S., Subbannayya, Y., ... Pandey, A. (2015). Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics, 15(2-3), 532-544. https://doi.org/10.1002/pmic.201400303

Quantitative phosphoproteomic analysis of IL-33-mediated signaling. / Pinto, Sneha M.; Nirujogi, Raja Sekhar; Rojas, Pamela Leal; Patil, Arun H.; Manda, Srikanth S.; Subbannayya, Yashwanth; Roa, Juan Carlos; Chatterjee, Aditi; Prasad, T. S.Keshava; Pandey, Akhilesh.

In: Proteomics, Vol. 15, No. 2-3, 01.01.2015, p. 532-544.

Research output: Contribution to journalArticle

Pinto, SM, Nirujogi, RS, Rojas, PL, Patil, AH, Manda, SS, Subbannayya, Y, Roa, JC, Chatterjee, A, Prasad, TSK & Pandey, A 2015, 'Quantitative phosphoproteomic analysis of IL-33-mediated signaling', Proteomics, vol. 15, no. 2-3, pp. 532-544. https://doi.org/10.1002/pmic.201400303
Pinto SM, Nirujogi RS, Rojas PL, Patil AH, Manda SS, Subbannayya Y et al. Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics. 2015 Jan 1;15(2-3):532-544. https://doi.org/10.1002/pmic.201400303
Pinto, Sneha M. ; Nirujogi, Raja Sekhar ; Rojas, Pamela Leal ; Patil, Arun H. ; Manda, Srikanth S. ; Subbannayya, Yashwanth ; Roa, Juan Carlos ; Chatterjee, Aditi ; Prasad, T. S.Keshava ; Pandey, Akhilesh. / Quantitative phosphoproteomic analysis of IL-33-mediated signaling. In: Proteomics. 2015 ; Vol. 15, No. 2-3. pp. 532-544.
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