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. 2023 Apr 13;19(5):289–304. doi: 10.1038/s41582-023-00800-7

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Fig. 1 — Bruton tyrosine kinase (BTK) mediates signalling from the B cell receptor (BCR) in B cells and IgG Fc receptor III (FcγRIII, also known as CD16) in macrophages and microglia to downstream elements crucial to immune cell function. a, BCR activation leads to the formation and activation of a signalling complex in which BTK is linked with 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase-γ2 (PLCγ2) through the scaffold protein SLP65 (Src homology 2 domain-containing leukocyte protein of 65 kDa). Phosphorylation of PLCγ2 by BTK triggers several downstream signalling pathways, including inositol 1,4,5-triphosphate (IP₃) receptor (IP3R)-dependent calcium mobilization (green), cytoskeletal remodelling (light blue) and activation of nuclear factor of activated T cells (NFAT; green), nuclear factor (NF)-κB (olive green) and RAS GTPase pathways (red). b, FcγRIII activation recruits and activates Lck/Yes-related novel protein tyrosine kinase (LYN) and spleen tyrosine kinase (SYK), which phosphorylate linker for the activation of T cells family member 1 (LAT) and establish a signalling complex comprising BTK and PLCγ2. In turn, PLCγ2 is responsible for generating diacylglycerol and IP₃, two secondary messengers that control cellular effector responses via protein kinase Cβ (PKC-β) and intracellular Ca²⁺ release, respectively. Diacylglycerol interacts with a scaffold complex comprising B cell leukaemia and/or lymphoma 10 (BCL10), B cell adaptor for phosphoinositide-3-kinase (BCAP) and caspase recruitment domain-containing protein 11 (CARD11). ER, endoplasmic reticulum; ERK, extracellular signal-regulated protein kinase; ITAM, immunoreceptor tyrosine-based activation motif; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; PI3K, phosphoinositide 3-kinase; PtdIns(4,5)P₂, phosphatidylinositol 4,5-bisphosphate; PtdIns(3,4,5)P₃, phosphatidylinositol (3,4,5)-trisphosphate; TRAF6, tumour necrosis factor receptor-associated factor 6; WASP, Wiskott–Aldrich syndrome protein. Adapted from refs. ^57,210, Springer Nature.