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Selective phosphorylation during early macrophage differentiation
Author(s) -
Zhang Huoming,
Qian PeiYuan,
Ravasi Timothy
Publication year - 2015
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201400511
Subject(s) - stable isotope labeling by amino acids in cell culture , biology , cellular differentiation , proteomics , microbiology and biotechnology , transcriptome , phosphorylation , quantitative proteomics , protein phosphorylation , computational biology , gene expression , gene , genetics , protein kinase a
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.