Spleen tyrosine kinase (SYK)

An intracellular cytoplasmic tyrosine kinase that is an important mediator of immunoreceptor signaling in macrophages, neutrophils, mast cells and B cells.

Present in synovium of patients with rheumatoid arthritis.

Its activation is important for cytokine and metalloproteinase production induced by tumor necrosis factor-alpha in fibroblast-like synoviocytes from rheumatoid arthritis patients.

Inhibition of SYK activity reduces rheumatoid arthritis activity.

Spleen tyrosine kinase, known as Syk, is an enzyme which in humans is encoded by the SYK gene.

Gene location on Chromosome 9.

SYK Band 9q22

SYK, along with Zap-70, is a member of the Syk family of tyrosine kinases.

Syk and Zap-70 are primarily expressed in hematopoietic tissues.

Syk is expressed in a variety of tissues.

Syk transmits signals from the B-Cell receptor, and from a variety of cell surface receptors including CD74, Fc Receptor, and integrins.

Abnormal function of Syk has been linked to hematopoeitic malignancies including translocations involving Itk and Tel.

Several transforming viruses contain Immunoreceptor Tyrosine Activation Motifs, which lead to activation of Syk including Epstein Barr virus, bovine leukemia virus, and mouse mammary tumor virus.

Has a central role in transmission of activating signals within B-cells and the suppression of this tyrosine kinase might aid in the treatment of B cell malignancies and autoimmune diseases.

The orally active SYK inhibitor fostamatinib is used 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.

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