SYK

GeneName

SYK

Summary

SYK, also known as spleen tyrosine kinase or p72 Syk, is a 72kDa non-receptor tyrosine kinase predominantly expressed in immune cells such as B cells and myeloid cells. It is localised in various cellular compartments including the cytoplasm, nucleus, and plasma membrane. SYK plays a crucial role in the B cell receptor and T cell receptor signalling pathways, mediating downstream signalling events that lead to cellular activation, differentiation, and immune responses. Its kinase activity is essential for processes such as B cell differentiation, leukocyte activation, and the adaptive immune response, as well as in the clearance of amyloid-beta and regulation of inflammation.

Importance

SYK is relevant to: - The modulation of immune responses, making it a potential target for therapies in autoimmune diseases and immunotherapy. - The role in B cell receptor signalling, which is critical for the development of B cell malignancies. - Its involvement in phagocytosis and neutrophil activation, linking it to innate immunity and host defence mechanisms. - The regulation of inflammatory responses, which has implications in chronic inflammatory conditions and tissue homeostasis.

Top Products

For researchers investigating SYK, we highly recommend the top-selling recombinant antibody, Anti-Syk antibody [EP573Y] (ab40781). This antibody has been validated in knockout models, ensuring reliable performance in your experiments. It is particularly effective for Western blotting (WB) and immunohistochemistry (IHC), making it a versatile choice for various applications. With 28 citations, this antibody is well-regarded in the research community, reflecting its trustworthiness and efficacy in SYK studies.

Abcam Product Citation Summary

The data indicates that SYK is being studied in the context of renal epithelial-mesenchymal transition and its involvement in the Syk/TGF-β1/Smad signalling pathway, as well as in the response of human fibroblast cells to HCMV infection. The use of western blotting suggests a focus on protein expression levels in these biological contexts.

Abcam Product Citation Table

Domain

The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization.

Function

Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity).

Involvement in disease

Immunodeficiency 82 with systemic inflammation

IMD82

An autosomal dominant immunologic disorder with onset in early childhood. It is characterized by recurrent infections with various organisms, and multi-organ inflammation that manifests as colitis, hepatitis, arthritis and dermatitis. Patients have a propensity for the development of lymphoma, usually in adulthood. Disease severity is variable.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.

Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-323 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-348 creates a binding site for VAV1. Phosphorylation on Tyr-348 and Tyr-352 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway (By similarity). Phosphorylated on tyrosine residues in response to IL15 (PubMed:15123770). Phosphorylation on Ser-297 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG. Phosphorylation at Tyr-630 creates a binding site for BLNK. Dephosphorylated by PTPN6.

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.

Tissue Specificity

Widely expressed in hematopoietic cells (at protein level) (PubMed:8163536). Expressed in neutrophils (at protein level) (PubMed:15123770). Within the B-cell compartment, expressed from pro- and pre-B cells to plasma cells (PubMed:8163536).

Cellular localization

• Cell membrane
• Cytoplasm
• Cytosol

Alternative names

Tyrosine-protein kinase SYK, Spleen tyrosine kinase, p72-Syk, SYK

Database links

swissprot:P43405 omim:600085 entrezGene:6850

Other research areas

• Cardiovascular
• Immuno-oncology
• Neuroscience