Blockage of the immune complex-triggered transmembrane proximity between complement receptor type 3 and microfilaments by staurosporine and methyl-2,5-dihydroxycinnamate

Abstract

Recent studies have suggested that integrin (CR3) participates in the signal transduction pathways of certain GPI-anchored phagocytic receptors including FcγRIIIB. One consequence of this functional linkage is an inducible association between CR3 and cortical microfilaments that is triggered by FcγRIIIB binding to immobilized immune complexes (IC). That this signaling event requires the co-expression of FcγRIIIB with CR3 was documented by the use of NIH 3T3 transfectants expressing both CR3 and FcγRIIIB (clone 3-23), CR3 alone (clone 3-19), and FcγRIIIB alone (clone 3-15). Pretreatment of 3-23 cells with protein kinase inhibitors such as staurosporine and methyl 2,5-dihydroxycinnamate (MDHC) blocked IC-stimulated CR3-microfilament proximity without affecting the extent to which FcγRIIIB constrains the lateral membrane mobility of a subset of CR3 on the cell surface (as measured in fluorescence recovery after photobleaching experiments). These data support that CR3 and FcγRIIIB molecules are physically and functionally associated and that ligation of FcgRIIIB triggers CR3-dependent signal transduction.