Figure 1.

FcR signaling (e.g., FcγRII). (Left), the aggregation by an immune complex of FcR bearing ITAM motif (e.g. FcγRIIA) induces phosphorylation of the two ITAM tyrosine residues by Src kinases Lyn and Fyn responsible for recruitment and phosphorylation of Syk inducing cellular activation through PLCγ and PI3K signaling pathways. The PLCγ converts PI(4,5)P₂ into IP₃ and DAG. IP₃, a soluble inositol phosphate, leads to Ca²⁺ mobilization while DAG activate MAPK.PI3K converts PI(4,5)P₂ to PI(3,4,5)P₃ allowing recruitment of signal intermediates through their pleckstrin homology (PH) domain (Middle), co-ligation between an activating heterologous receptor (e.g., the BCR) and the inhibitory FcR (i.e., FcγRIIB) induces phosphorylation of the tyrosine present within the ITIM motif by Lyn (5), leading to the phosphorylation and recruitment of phosphatases (SHIP or SHP). The phosphatases PTEN and SHIP1/2 regulate cellular levels of PI(3,4,5)P₃ by hydrolyzing it to PI(4,5)P₂ and PI(3,4)P₂, respectively. These dephosphorylations inhibit cell proliferation. (Right), monovalent targeting of FcR bearing ITAM motif (e.g., FcγRIIA) induces the phosphorylation of the last tyrosine residue of the ITAM motif by Lyn responsible for transient recruitment of Syk followed by that of SHP-1 which abrogates the activation signal.