RRC ID 52847
著者 Chihara K, Kato Y, Yoshiki H, Takeuchi K, Fujieda S, Sada K.
タイトル Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression in U937 cells.
ジャーナル Sci Rep
Abstract The adaptor protein c-Abl SH3 domain binding protein-2 (3BP2) is tyrosine phosphorylated by Syk in response to cross-linking of antigen receptors, which in turn activates various immune responses. Recently, a study using the mouse model of cherubism, a dominant inherited disorder caused by mutations in the gene encoding 3BP2, showed that 3BP2 is involved in the regulation of phagocytosis mediated by Fc receptor for IgG (FcγR) in macrophages. However, the molecular mechanisms underlying 3BP2-mediated regulation of phagocytosis and the physiological relevance of 3BP2 tyrosine phosphorylation remains elusive. In this study, we established various gene knockout U937 cell lines using the CRISPR/Cas9 system and found that 3BP2 is rapidly tyrosine phosphorylated by Syk in response to cross-linking of FcγRI. Depletion of 3BP2 caused significant reduction in the Fc receptor γ chain (FcRγ)-mediated phagocytosis in addition to the FcγRI-mediated induction of chemokine mRNA for IL-8, CCL3L3 and CCL4L2. Syk-dependent tyrosine phosphorylation of 3BP2 was required for overcoming these defects. Finally, we found that the PH and SH2 domains play important roles on FcγRI-mediated tyrosine phosphorylation of 3BP2 in HL-60 cells. Taken together, these results indicate that Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression.
巻・号 7(1)
ページ 11480
公開日 2017-9-13
DOI 10.1038/s41598-017-11915-5
PII 10.1038/s41598-017-11915-5
PMID 28904407
PMC PMC5597638
MeSH Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Amino Acid Sequence Chemokines / genetics* Chemokines / metabolism Gene Expression Regulation* Humans Mutation Phagocytosis* Phosphorylation Protein Binding Protein Interaction Domains and Motifs Receptors, Fc / chemistry Receptors, Fc / genetics Receptors, Fc / metabolism* Syk Kinase / chemistry Syk Kinase / genetics Syk Kinase / metabolism* Tyrosine / metabolism* U937 Cells src Homology Domains
IF 3.998
引用数 5
リソース情報
遺伝子材料 pX330-FcR gamma gRNA (RDB15903) pX330-Syk gRNA (RDB15904) pX330-Hck gRNA (RDB15905) pX330-Abl gRNA (RDB15906) pX330-3BP2 gRNA (RDB15907).