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. Author manuscript; available in PMC: 2016 Mar 8.
Published in final edited form as: Nat Rev Immunol. 2010 Jun;10(6):387–402. doi: 10.1038/nri2765

Figure 5. Non-immune functions of SYK.

Figure 5

a ∣ The role of DAP12 and FcRγ in osteoclasts. In addition to a RANK–RANK ligand interaction, osteoblasts also express yet unidentified ligands that engage a putative FcR-associated receptor (most likely OSCAR or PIR-A) on the osteoclast surface. Osteoclasts also express putative DAP12-associated receptors (most likely TREM2) which bind to yet unidentified ligands that are not expressed by osteoblasts. Both FcRγ and DAP12 promote osteoclast development and function through ITAM-mediated SYK activation and the PLCγ2-Calcineurin-NFATc1 pathway. Inset: Mechanism of osteoclast development. Osteoclasts develop from myeloid progenitors re-programmed by osteoblast-derived RANK ligand, leading to biochemical differentiation. Pre-osteoclasts then fuse to generate mature multi-nucleated osteoclasts and resorb the bone surface. αVβ3 integrins are required for sealing the resorption area. b ∣ SYK-mediated signaling in platelets. Collagen activates the FcRγ-associated GpVI receptor on platelets and triggers Syk activation by an ITAM-mediated manner. The snake venom rhodocytin, the endogenous podoplanin and possible other platelet agonists activate the CLEC2 receptor which recruits SYK to phosphorylated tyrosine in the CLEC2 hemITAMs at a 2:1 stoichiometry. Fibrinogen engages the αIIbβ3 integrin which associates with the ITAM-containing FcγRIIA receptor. This complex likely activates SYK through both conventional ITAM-mediated SYK activation pathways and by binding of the integrin β-chain to the N-terminal SH2-domain of SYK in a phosphotyrosine-independent manner. All three cases of SYK activation lead to platelet activation through PLCγ2. c ∣ The role of SYK in separation of blood and lymphatic vessels. Lymphatic vessels express podoplanin which trigger platelet activation and aggregation. This and possible other mechanisms (“?”) lead to closing off any blood-lymphatic shunts. The mechanism of podoplanin-mediated platelet activation involves the CLEC2 receptor which activates SYK through hemITAM phosphorylation, as well as SLP76 and PLCγ2 acting downstream of SYK.