Summary

Name SYK
Full Name Tyrosine-protein kinase SYK
Synonyms Spleen tyrosine kinase, p72-Syk
Primary ID P43405
Links - -
Type protein
Relations 45
Inhibitors Fostamatinib disodium; R406; 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)-4-pyrimidinyl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one
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. 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 VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. 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. 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 plays also a role in T-cell receptor signaling. Plays also 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. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also 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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation SYK 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IKZF1 0.14
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SNCA 0.14
Publications: 3 Organism: Homo Sapiens
Tissue: Ovary, Brain
+ up-regulates activity img/direct-activation.png phosphorylation SYK 0.35
Publications: 6 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SH3BP2 0.22
Publications: 3 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation BLNK 0.38
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation LCK 0.36
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SLC4A1 0.14
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation SLC4A1 0.14
Publications: 2 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation IL15RA 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation FCGR2A 0.22
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation SHC1 0.38
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HCLS1 0.14
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAP4K1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TUBA4A 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BTK 0.44
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PRKCA 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PLCG1 0.6
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition SYK 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition SYK 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation VAV1 0.58
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition SYK 0.14
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png dephosphorylation SYK 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding SYK 0.49
Publications: 1 Organism: Homo Sapiens