Syk

1A81, 1CSY, 1CSZ, 1XBA, 1XBB, 1XBC, 3BUW, 3EMG, 3FQE, 3FQH, 3FQS, 3SRV, 3TUB, 3TUC, 3TUD, 3VF8, 3VF9, 4DFL, 4DFN, 4F4P, 4FL1, 4FL2, 4FL3, 4FYN, 4FYO, 4FZ6, 4FZ7, 4GFG, 4I0R, 4I0S, 4I0T, 4PUZ, 4PV0, 4PX6, 4RX7, 4RX8, 4RX9, 5CXH, 5CXZ, 5CY3, 4XG6, 4XG2, 4XG3, 4XG8, 4XG7, 4YJR, 4YJP, 5C27, 4RSS, 4XG4, 5C26, 4YJV, 4YJO, 4WNM, 4YJT, 4YJU, 4YJS, 4XG9, 5GHV685020963ENSG00000165025ENSMUSG00000021457P43405P48025NM_001135052NM_001174167NM_001174168NM_003177NM_001198977NM_011518NP_001128524NP_001167638NP_001167639NP_003168NP_001185906NP_035648Spleen tyrosine kinase, also known as Syk, is an enzyme which in humans is encoded by the SYK gene.1a81: CRYSTAL STRUCTURE OF THE TANDEM SH2 DOMAIN OF THE SYK KINASE BOUND TO A DUALLY TYROSINE-PHOSPHORYLATED ITAM1csy: SYK TYROSINE KINASE C-TERMINAL SH2 DOMAIN COMPLEXED WITH A PHOSPHOPEPTIDEFROM THE GAMMA CHAIN OF THE HIGH AFFINITY IMMUNOGLOBIN G RECEPTOR, NMR1csz: SYK TYROSINE KINASE C-TERMINAL SH2 DOMAIN COMPLEXED WITH A PHOSPHOPEPTIDEFROM THE GAMMA CHAIN OF THE HIGH AFFINITY IMMUNOGLOBIN G RECEPTOR, NMR1xba: Crystal structure of apo syk tyrosine kinase domain1xbb: Crystal structure of the syk tyrosine kinase domain with Gleevec1xbc: Crystal structure of the syk tyrosine kinase domain with Staurosporin Spleen tyrosine kinase, also known as Syk, is an enzyme which in humans is encoded by the SYK gene. SYK, along with Zap-70, is a member of the Syk family of tyrosine kinases. These non-receptor cytoplasmic tyrosine kinases share a characteristic dual SH2 domain separated by a linker domain. However, activation of SYK relies less on phosphorylation by Src family kinases than Zap-70. While Syk and Zap-70 are primarily expressed in hematopoietic tissues, there is expression of Syk in a variety of tissues. Within B and T cells respectively, Syk and Zap-70 transmit signals from the B-Cell receptor and T-Cell receptor. Syk plays a similar role in transmitting signals from a variety of cell surface receptors including CD74, Fc Receptor, and integrins. Mice that lack Syk completely (Syk−/−, Syk-knockout) die during embryonic development around midgestation. They show severe defects in the development of the lymphatic system. Normally, the lymphatic system and the blood system are strictly separated from each other. However, in Syk deficient mice the lymphatics and the blood vessels form abnormal shunts, leading to leakage of blood into the lymphatic system. The reason for this phenotype was identified by a genetic fate mapping approach, showing that Syk is expressed in myeloid cells which orchestrate the proper separation of lymphatics and blood system during embryogenesis and beyond. Thus, Syk is an essential regulator of the lymphatic system development in mice. Abnormal function of Syk has been implicated in several instances of hematopoeitic malignancies including translocations involving Itk and Tel. Constitutive Syk activity can transform B cells. Several transforming viruses contain 'Immunoreceptor Tyrosine Activation Motifs' (ITAMs) which lead to activation of Syk including Epstein Barr virus, bovine leukemia virus, and mouse mammary tumor virus. Given the central role of SYK in transmission of activating signals within B-cells, a suppression of this tyrosine kinase might aid in the treatment of B cell malignancies and autoimmune diseases. Syk inhibition has been proposed as a therapy for both lymphoma and chronic lymphocytic leukemia. Syk inhibitors are in clinical development, including cerdulatinib and entospletinib. Other inhibitors of B-cell receptor (BCR) signaling including ibrutinib (PCI-32765) which inhibits BTK, and idelalisib (PI3K inhibitor - CAL-101 / GS-1101) showed activity in the diseases as well. The orally active SYK inhibitor fostamatinib (R788) in the treatment of rheumatoid arthritis. The Syk inhibitor nilvadipine has been shown to regulate amyloid-β production and Tau phosphorylation and hence has been proposed as a treatment for Alzheimer's Disease and has entered phase III clinical trials.