PMID- 18710945 OWN - NLM STAT- MEDLINE DCOM- 20081024 LR - 20240415 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 28 IP - 20 DP - 2008 Oct TI - Regulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages. PG - 6149-59 LID - 10.1128/MCB.00220-08 [doi] AB - 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. FAU - Achuthan, Adrian AU - Achuthan A AD - Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia. FAU - Masendycz, Paul AU - Masendycz P FAU - Lopez, Jamie A AU - Lopez JA FAU - Nguyen, Thao AU - Nguyen T FAU - James, David E AU - James DE FAU - Sweet, Matthew J AU - Sweet MJ FAU - Hamilton, John A AU - Hamilton JA FAU - Scholz, Glen M AU - Scholz GM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080818 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Enzyme Inhibitors) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Qa-SNARE Proteins) RN - 17885-08-4 (Phosphoserine) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Amino Acid Sequence MH - Animals MH - Computational Biology MH - Endosomes/drug effects/enzymology/*metabolism MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Female MH - Macrophage Colony-Stimulating Factor/*pharmacology MH - Macrophages/*drug effects/enzymology/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Models, Biological MH - Molecular Sequence Data MH - Mutation/genetics MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation/drug effects MH - Phosphoserine/metabolism MH - Protein Binding/drug effects MH - Protein Kinase C/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Qa-SNARE Proteins/chemistry/genetics/*metabolism MH - Up-Regulation/drug effects PMC - PMC2577439 EDAT- 2008/08/20 09:00 MHDA- 2008/10/25 09:00 PMCR- 2009/04/01 CRDT- 2008/08/20 09:00 PHST- 2008/08/20 09:00 [pubmed] PHST- 2008/10/25 09:00 [medline] PHST- 2008/08/20 09:00 [entrez] PHST- 2009/04/01 00:00 [pmc-release] AID - MCB.00220-08 [pii] AID - 0220-08 [pii] AID - 10.1128/MCB.00220-08 [doi] PST - ppublish SO - Mol Cell Biol. 2008 Oct;28(20):6149-59. doi: 10.1128/MCB.00220-08. Epub 2008 Aug 18.