Document Detail

Serine phosphorylation of FcγRI cytoplasmic domain directs lipid raft localization and interaction with protein 4.1G.
MedLine Citation:
PMID:  22003208     Owner:  NLM     Status:  MEDLINE    
The high-affinity IgG receptor (CD64, FcγRI) has several special capacities, including the receptor-stimulated cleavage of the cell surface B cell-activating factor of the TNF superfamily (TNFSF13B). With the use of the yeast two-hybrid system, we and others have shown that FcγRI interacts with protein 4.1G (EPB41L2). Our mutational analyses identified two required 4.1G-interacting regions in the FcγRI CY and one FcγRI-interacting site in the C-terminus of protein 4.1G. Herein, we explore mechanism(s) that may regulate the interaction between protein 4.1G and FcγRI CY and influence FcγRI membrane mobility and function. We show that FcγRI CY interacts with protein 4.1G in vitro and that FcγRI coimmunoprecipitates protein 4.1G in freshly isolated human PBMC. With the use of immunostaining, we show that FcγRI colocalizes with protein 4.1G in unstimulated U937 cells, in which the FcγRI CY is constitutively serine-phosphorylated, but significant uncoupling occurs following FcγRI cross-linking, suggesting phosphoserine-regulated interaction. In vitro, protein 4.1G interacted preferentially with CK2-phosphorylated FcγRI CY, and compared with WT FcγRI, a nonphosphorylatable FcγRI mutant receptor was excluded from lipid rafts, suggesting a key role for protein 4.1G in targeting phosphorylated FcγRI to rafts. These data are consistent with a phosphoserine-dependent tethering role for protein 4.1G in maintaining FcγRI in lipid rafts and provide insight into the unique phosphoserine-based regulation of receptor signaling by FcγRI CY.
Andrew W Gibson; Xinrui Li; Jianming Wu; Julie G Baskin; Chander Raman; Jeffrey C Edberg; Robert P Kimberly
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-14
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  91     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-04     Completed Date:  2012-02-27     Revised Date:  2014-09-03    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  97-103     Citation Subset:  IM    
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MeSH Terms
Alanine / genetics
Amino Acid Substitution / genetics
Cytoplasm / immunology,  metabolism
Cytoskeletal Proteins / metabolism*
Gene Library
Leukocytes, Mononuclear / cytology*,  immunology,  metabolism*
Membrane Microdomains / immunology,  metabolism*
Membrane Proteins / metabolism*
Phosphorylation / immunology
Phosphoserine / metabolism*
Protein Binding / genetics,  immunology
Protein Structure, Tertiary / genetics
Receptors, IgG / chemistry,  metabolism*
U937 Cells
Grant Support
Reg. No./Substance:
0/Cytoskeletal Proteins; 0/FCGR1A protein, human; 0/Membrane Proteins; 0/Receptors, IgG; 0/erythrocyte membrane band 4.1 protein; 17885-08-4/Phosphoserine; OF5P57N2ZX/Alanine

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