Phagocytosis: A Fundamental Process in Immunity

Figure 1

Fcγ receptor signal transduction. FcγRIIa crosslinking by immunoglobulin (IgG) bound to a particle induces activation of Src family kinases (SFK), which phosphorylate tyrosine residues in the ITAMs (red box) of the cytoplasmic tail of the receptor. Then, Syk associates with phosphorylated ITAMs and leads to phosphorylation and activation of a signaling complex formed by the scaffold protein LAT (linker for activation of T cells) interacting with various proteins. Some of these proteins are phospholipase C gamma (PLCγ), which produces inositoltrisphosphate (IP₃) and diacylglycerol (DAG). These second messengers cause calcium release and activation of protein kinase C (PKC), respectively. PKC leads to activation of extracellular signal-regulated kinases (ERK and p38). The guanine nucleotide exchange factor Vav activates the GTPase Rac, which is involved in regulation of the actin nucleation complex Arp2/3, via the nucleation-promoting factor Scar/WAVE. Rac is also involved in activation of transcription factors such as NF- κB and JNK. The enzyme phosphatidylinositol 3-kinase (PI3K), which is recruited and activated by Syk, generates the lipid phosphatidylinositol-3,4,5-trisphosphate (PIP₃) at the phagocytic cup. This lipid also regulates Rac activation and contractile proteins such as myosin. Another GTPase, Cdc42, is also activated during FcγR signaling by an unknown mechanism and induces actin polymerization by activating the nucleation-promoting factor WASp (Wiskott-Aldrich Syndrome protein). P represents a phosphate group. ER, endoplasmic reticulum.