| First Author | Achuthan A | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 20 | Pages | 6149-59 |
| PubMed ID | 18710945 | Mgi Jnum | J:140965 |
| Mgi Id | MGI:3814969 | Doi | 10.1128/MCB.00220-08 |
| Citation | Achuthan A, et al. (2008) Regulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages. Mol Cell Biol 28(20):6149-59 |
| abstractText | Colony-stimulating factor 1 (CSF-1) is the main growth factor controlling the development of macrophages from myeloid progenitor cells. However, CSF-1 also regulates some of the key effector functions of macrophages (e.g., phagocytosis and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates vesicle trafficking events involved in phagocytosis and cytokine secretion. Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1 upregulated Stx7 expression in primary mouse macrophages; it also upregulated expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF-1 induced the rapid serine phosphorylation of Stx7 and enhanced its binding to Vti1b, Stx8, and VAMP8. Bioinformatics analysis and results from experiments with kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was mediated by protein kinase C and Akt in response to phosphatidylinositol 3-kinase activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues in the Habc domain and/or 'linker' region of Stx7. Thus, CSF-1 is a key regulator of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1 on Stx7 may provide a mechanism for the regulation of macrophage effector functions by CSF-1. |
