Global Phosphoproteomics Unveils Kinase-Regulated Networks in Systemic Lupus Erythematosus

Meng, Shuhui1,2,3; Li, Teng1; Wang, Tingting3; Li, Dandan1,2; Chen, Jieping1; Li, Heng2,3; Cai, Wanxia1,2; Zeng, Zhipeng1,2; Liu, Dongzhou3; Tang, Donge1,2; Hong, Xiaoping3; Dai, Yong1,2

2022-12-01

10.1016/j.mcpro.2022.100434

MOLECULAR & CELLULAR PROTEOMICS   Impact Factor & Quartile

1535-9484

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune complex deposition in multiple organs. Despite the severe symptoms caused by it, the underlying mechanisms of SLE, especially phosphorylation-dependent regulatory networks remain elusive. Herein, by combining high-throughput phospho-proteomics with bioinformatics approaches, we estab-lished the global phosphoproteome landscape of the peripheral blood mononuclear cells from a large number of SLE patients, including the remission stage (SLE_S), active stage (SLE_A), rheumatoid arthritis, and healthy controls, and thus a deep mechanistic insight into SLE signaling mechanism was yielded. Phosphorylation upregulation was preferentially in patients with SLE (SLE_S and SLE_A) compared with healthy controls and rheumatoid arthritis populations, resulting in an atypical enrichment in cell adhesion and migration signatures. Several specifically upregulated phosphosites were identified, and the leuko-cyte transendothelial migration pathway was enriched in the SLE_A group by expression pattern clustering analysis. Phosphosites identified by 4D-label-free quantification unveiled key kinases and kinase-regulated networks in SLE, then further validated by parallel reaction monitoring. Some of these validated phosphosites including vinculin S275, vinculin S579 and transforming growth factor beta-1 -induced transcript 1 S68, primarily were phosphorylation of Actin Cytoskeleton-related proteins. Some predicted ki-nases including MAP3K7, TBK1, IKK beta, and GSK3 beta, were validated by Western blot using kinases phosphorylation sites-specific antibodies. Taken together, the study has yielded fundamental insights into the phosphosites, ki-nases, and kinase-regulated networks in SLE. The map of the global phosphoproteomics enables further under-standing of this disease and will provide great help for seeking more potential therapeutic targets for SLE.

SCI

English

Corresponding

science and technology plan of Shenzhen[JCYJ20200109144218597] ; group of Rheumatology and Immunology[SZSM202111006] ; National Natural Science Foundation of China[81971464]

Biochemistry & Molecular Biology

Biochemical Research Methods

WOS:000917354500008

ELSEVIER

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Jinan Univ, Clin Med Res Ctr, Guangdong Prov Engn Res Ctr Autoimmune Dis Precis, Shenzhen Engn Res Ctr Autoimmune Dis, Shenzhen, Guangdong, Peoples R China
2.Jinan Univ, Clin Med Coll 2, Dept Rheumatol & Immunol, Shenzhen, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China

Meng, Shuhui,Li, Teng,Wang, Tingting,et al. Global Phosphoproteomics Unveils Kinase-Regulated Networks in Systemic Lupus Erythematosus[J]. MOLECULAR & CELLULAR PROTEOMICS,2022,21(12).

Meng, Shuhui.,Li, Teng.,Wang, Tingting.,Li, Dandan.,Chen, Jieping.,...&Dai, Yong.(2022).Global Phosphoproteomics Unveils Kinase-Regulated Networks in Systemic Lupus Erythematosus.MOLECULAR & CELLULAR PROTEOMICS,21(12).

Meng, Shuhui,et al."Global Phosphoproteomics Unveils Kinase-Regulated Networks in Systemic Lupus Erythematosus".MOLECULAR & CELLULAR PROTEOMICS 21.12(2022).