The cytoplasmic region of mouse Fc gamma RIIb1, but not Fc gamma RIIb2, binds phospholipid membranes

The cytoplasmic regions of the mouse low-affinity Fc gamma RII isoforms, Fc gamma RIIb1 and Fc gamma RIIb2, play key roles in signal transduction by m ediating different cellular functions. The Fc gamma RIIb1 (94 residues) and Fc gamma RIIb2 (47 residues) cytoplasmic regions are generated by differen tial mRNA splicing in which a single aspartic acid residue in Fc gamma RIIb 2 is replaced by a 48-residue insert in Fc gamma RIIb1, In previous work, q uantities of the mFc gamma RIIb1 and mFc gamma RIIb2 cytoplasmic regions we re generated, and their secondary structures were examined in different sol utions with circular dichroism [Chen, L., Thompson, N. L., and Pielak, G. J . (1997) Protein Sci. 6, 1038-1046]. In the work described here, steady-sta te light scattering was used to investigate possible interactions of the tw o isolated cytoplasmic regions with phospholipid vesicles. Three phospholip id compositions were examined: phosphatidylserine/phosphatidylcholine (PSI PC) (25/75, mol/mol); phosphatidylinositol bisphosphate/phosphatidylcholine (PIP2/PC) (25/75, mol/mol); and pure phosphatidylcholine (PC), Binding was examined in the presence and absence of Ca2+. The mFc gamma RIIb1 cytoplas mic peptide binds PS/PC vesicles weakly in the absence of Ca2+ and more str ongly in the presence of Ca2+. For PIP2/PC vesicles, the behavior is revers ed; binding is weak in the presence of Ca2+ and stronger in its absence. Th e mFc gamma RIIb1 peptide also weakly binds pure PC vesicles, in a Ca2+-ind ependent manner. The mFc gamma RIIb2 cytoplasmic peptide does not bind, in the presence or absence of Ca2+, to PS/PC, PIP2/PC or PC vesicles. The impl ications of these results for the mechanisms of signal transduction mediate d by the two mFc gamma RII cytoplasmic regions are discussed.