Document Detail

Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface.
MedLine Citation:
PMID:  16720734     Owner:  NLM     Status:  MEDLINE    
Annexin A1 (ANXA1) has an important role in cell-cell communication in the host defense and neuroendocrine systems. In both systems, its actions are exerted extracellularly via membrane-bound receptors on adjacent sites after translocation of the protein from the cytoplasm to the cell surface of adjacent cells. This study used molecular, microscopic, and pharmacological approaches to explore the mechanisms underlying the cellular exportation of ANXA1 in TtT/GF (pituitary folliculo-stellate) cells. LPS caused serine-phosphorylation of ANXA1 (ANXA1-S27-PO4) and translocation of the phosphorylated protein to the cell membrane. The fundamental requirement of phosphorylation for membrane translocation was confirmed by immunofluorescence microscopy on cells transfected with wild-type or mutated (S27/A) ANXA1 constructs tagged with enhanced green fluorescence protein. The trafficking of ANXA1-S27-PO4 to the cell surface was dependent on PI3-kinase and MAP-kinase. It also required HMG-coenzyme A and myristoylation. The effects of HMG-coenzyme A blockade were overcome by mevalonic acid (the product of HMG-coenzyme A) and farnesyl-pyrophosphate but not by geranyl-geranylpyrophosphate or cholesterol. Together, these results suggest that serine-27 phosphorylation is essential for the translocation of ANXA1 across the cell membrane and also identify a role for isoprenyl lipids. Such lipids could target consensus sequences in ANXA1. Alternatively, they may target other proteins in the signal transduction cascade (e.g., transporters).
E Solito; H C Christian; M Festa; A Mulla; T Tierney; R J Flower; J C Buckingham
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-23
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  20     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-03     Completed Date:  2006-07-31     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1498-500     Citation Subset:  IM    
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, Du Cane Rd., London W12 0NN, UK.
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MeSH Terms
Annexin A1 / genetics,  metabolism*
Cell Communication
Cell Line, Tumor
Cell Membrane / metabolism*
Cytoplasm / metabolism
Enzyme Inhibitors / pharmacology
Genes, Reporter
Lipopolysaccharides / pharmacology
Mevalonic Acid / pharmacology
Mutagenesis, Site-Directed
Pituitary Neoplasms
Protein Processing, Post-Translational*
Protein Transport
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Grant Support
040269//Wellcome Trust; N:069234/B/02/Z//Wellcome Trust
Reg. No./Substance:
0/Annexin A1; 0/Enzyme Inhibitors; 0/Lipopolysaccharides; 150-97-0/Mevalonic Acid

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