| First Author | Gibson AW | Year | 2012 |
| Journal | J Leukoc Biol | Volume | 91 |
| Issue | 1 | Pages | 97-103 |
| PubMed ID | 22003208 | Mgi Jnum | J:179612 |
| Mgi Id | MGI:5302760 | Doi | 10.1189/jlb.0711368 |
| Citation | Gibson AW, et al. (2012) Serine phosphorylation of FcgammaRI cytoplasmic domain directs lipid raft localization and interaction with protein 4.1G. J Leukoc Biol 91(1):97-103 |
| abstractText | The high-affinity IgG receptor (CD64, FcgammaRI) 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 FcgammaRI interacts with protein 4.1G (EPB41L2). Our mutational analyses identified two required 4.1G-interacting regions in the FcgammaRI CY and one FcgammaRI-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 FcgammaRI CY and influence FcgammaRI membrane mobility and function. We show that FcgammaRI CY interacts with protein 4.1G in vitro and that FcgammaRI coimmunoprecipitates protein 4.1G in freshly isolated human PBMC. With the use of immunostaining, we show that FcgammaRI colocalizes with protein 4.1G in unstimulated U937 cells, in which the FcgammaRI CY is constitutively serine-phosphorylated, but significant uncoupling occurs following FcgammaRI cross-linking, suggesting phosphoserine-regulated interaction. In vitro, protein 4.1G interacted preferentially with CK2-phosphorylated FcgammaRI CY, and compared with WT FcgammaRI, a nonphosphorylatable FcgammaRI mutant receptor was excluded from lipid rafts, suggesting a key role for protein 4.1G in targeting phosphorylated FcgammaRI to rafts. These data are consistent with a phosphoserine-dependent tethering role for protein 4.1G in maintaining FcgammaRI in lipid rafts and provide insight into the unique phosphoserine-based regulation of receptor signaling by FcgammaRI CY. |
