title: Selective phosphorylation during early macrophage differentiation.
abstract: The differentiation of macrophages from monocytes is a tightly controlled and complex biological process. Although numerous studies have been conducted using biochemical approaches or global gene/protein profiling, the mechanisms of the early stages of differentiation remain unclear. Here we used SILAC-based quantitative proteomics approach to perform temporal phosphoproteome profiling of early macrophage differentiation. We identified a large set of phosphoproteins and grouped them as PMA-regulated and non-regulated phosphoproteins in the early stages of differentiation. Further analysis of the PMA-regulated phosphoproteins revealed that transcriptional suppression, cytoskeletal reorganization and cell adhesion were among the most significantly activated pathways. Some key involved regulators of these pathways are mTOR, MYB, STAT1 and CTNNB. Moreover, we were able to classify the roles and activities of several transcriptional factors during different differentiation stages and found that E2F is likely to be an important regulator during the relatively late stages of differentiation. This study provides the first comprehensive picture of the dynamic phosphoproteome during myeloid cells differentiation, and identifies potential molecular targets in leukemic cells.
authors: Division of Biological and Environmental Sciences & Engineering, Division of Applied Mathematics and Computer Sciences, King Abdullah University of Science & Technology, Thuwal, Kingdom of Saudi Arabia.|Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
authors: Huoming
authors: H
authors: Zhang
authors: School of Science, Hong Kong University of Science and Technology, Hong Kong, P. R. China.
authors: Pei-Yuan
authors: PY
authors: Qian
authors: Division of Biological and Environmental Sciences & Engineering, Division of Applied Mathematics and Computer Sciences, King Abdullah University of Science & Technology, Thuwal, Kingdom of Saudi Arabia.
authors: Timothy
authors: T
authors: Ravasi
mesh_terms: D000595:Amino Acid Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000032:analysis* / Q000378:metabolism; D010766:Phosphorylation; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction
chemical_list: D010750:Phosphoproteins
keywords: Biomedicine; Leukemia; Monocyte-to-macrophage differentiation; Phosphoproteome