Dataset Information

Phosphoproteomics analysis of normal and mutated granulocyte colony stimulating factor receptors

ABSTRACT: Granulocyte colony stimulating factor receptor (G-CSFR) plays important role in the production of neutrophils from hematopoietic stem cells. Mutated form of the receptor has been directly associated with two distinct malignant phenotype in patients, e.g. acute myeloid leukemia (AML) and chronic neutrophilic leukemia (CNL). However, the signaling mechanism of the mutated G-CSFRs is not well understood. Here, we describe a comprehensive SILAC based quantitative phosphoproteomic analysis of the mutated G-CSFRs compared to the normal receptor using BaF3 cell line based in vitro model system. High pH reversed phase concatenation and Titanium Dioxide Spin Tip column were utilized to increase the dynamic range and detection of the phosphoproteome of G-CSFRs. The dataset was further analyzed using several computational and bioinformatics tools. Overall, this dataset is a first of any phosphoproteomics analysis of granulocyte colony stimulating factor receptors in the normal and disease associated mutations. We anticipate that our dataset will have a strong potential to decipher the phospho-signaling differences between the normal and malignant G-CSFR biology with therapeutic implications.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): B Cell, Cell Suspension Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Pankaj Dwivedi

LAB HEAD: Kenneth D. Greis

PROVIDER: PXD009311 | Pride | 2019-02-14

REPOSITORIES: Pride

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Publications

Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors.

Dwivedi Pankaj P Muench David E DE Wagner Michael M Azam Mohammad M Grimes H Leighton HL Greis Kenneth D KD

Scientific data 20190409 1

Granulocyte colony stimulating factor receptor (G-CSFR) plays an important role in the production of neutrophil granulocytes. Mutated G-CSFRs have been directly associated with two distinct malignant phenotypes in patients, e.g. acute myeloid leukemia (AML) and chronic neutrophilic leukemia (CNL). However, the signaling mechanism of the mutated G-CSFRs is not well understood. Here, we present a comprehensive SILAC-based quantitative phosphoserine and phosphothreonine dataset of the normal and mu ...[more]

PMID: 30967555

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Project description:Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, the differentially expressed proteins were identified. Methods: In this paper, human monocytes, macrophage colony-stimulating factor induced macrophages, and oxidized low-density lipoprotein induced foam cells were cultured, and tandem mass tag (TMT) labeling combined with mass spectrometry (MS) were performed to find associations between foam cell transformation and proteome profiles. Results: Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively, using a cutoff of 1.5-fold change. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus and upregulated DEPs of foam cells/macrophages mostly located in the plasma membrane and extracellular. Functional analysis of DEPs demonstrated that cholesterol metabolism related proteins were upregulated in foam cells, whereas the immune response-related proteins were downregulated in foam cells. The protein-interaction network showed that the DEPs with the highest interaction intensity between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions: This study for the first time to perform quantitative proteomic investigation by TMT labeling and LC-MS/MS to identify differentially expressed proteins in human monocyte, macrophage, and foam cell. The results confirmed cholesterol metabolism was upregulated in foam cells, while immune response was suppressed, which suggested that foam cells were not the population that promote inflammation. In addition, KEGG enrichment analysis and protein-protein interaction indicated that the differentially expressed proteins locating in the endoplasmic reticulum and lysosomes may be key targets to regulate foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism involved in the transformation of macrophages to foam cells.

Dataset Information

Phosphoproteomics analysis of normal and mutated granulocyte colony stimulating factor receptors

Publications

Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors.

Similar Datasets

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