SYK
Description
The SYK (spleen associated tyrosine kinase) is a protein-coding gene located on chromosome 9.
SYK may refer to:
SYK is a non-receptor tyrosine kinase that plays a crucial role in signal transduction downstream of various transmembrane receptors, including key immune receptors like the B-cell receptor (BCR). It regulates a wide range of biological processes, encompassing innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation, and vascular development. SYK assembles into signaling complexes with activated receptors at the cell membrane, facilitated by interactions between its SH2 domains and the receptor's tyrosine-phosphorylated ITAM domains. This association can be direct or mediated by adapter proteins harboring ITAM or partial hemITAM domains. SRC subfamily kinases typically phosphorylate ITAM domains upon receptor engagement, initiating the signaling cascade. Although less common, SYK can also participate in ITAM-independent signaling pathways. SYK directly phosphorylates a diverse set of downstream effectors, including DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2, and BLNK, contributing to various cellular responses. Initially identified as essential for BCR signaling, SYK is critical for B-cell maturation, particularly during the transition from pro-B to pre-B stages. Upon BCR engagement, SYK activates BLNK, an adapter protein that connects the activated BCR to downstream signaling components. Additionally, SYK phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates and regulates BTK activity in BCR-coupled signaling. Beyond its role in BCR signaling, SYK participates in T-cell receptor signaling and is central to the innate immune response to various pathogens, including fungi, bacteria, and viruses. For instance, SYK is activated by the membrane lectin CLEC7A, leading to immune cell activation and ROS production in response to fungal proteins. In the presence of pathogens, SYK activates the inflammasome and NF-κB-mediated transcription of chemokines and cytokines. SYK also regulates neutrophil degranulation and phagocytosis through the MAPK signaling cascade. It is required for IL15-induced neutrophil phagocytosis and mediates dendritic cell activation by cell necrosis stimuli. SYK is further involved in mast cell activation and basophil interleukin-3/IL3-mediated signaling. SYK also functions downstream of receptors mediating cell adhesion, relaying signals for integrin-mediated neutrophil and macrophage activation as well as P-selectin receptor/SELPG-mediated leukocyte recruitment to inflammatory sites. SYK also plays roles in non-immune processes, including vascular development, where it may regulate blood and lymphatic vascular separation. It is essential for osteoclast development and function. SYK functions in platelet activation by collagen, mediating PLCG2 phosphorylation and activation. It can be linked to the collagen receptor through the ITAM domain-containing FCER1G. SYK is also activated by the membrane lectin CLEC1B, which is required for platelet activation by PDPN/podoplanin. SYK is involved in platelet adhesion, being activated by ITGB3 upon engagement with fibrinogen. In collaboration with CEACAM20, SYK enhances CXCL8/IL-8 cytokine production via the NFKB pathway, potentially contributing to the intestinal immune response.
SYK is also known as IMD82, p72-Syk.
