The spleen tyrosine kinase (Syk) in human disease, implications for design of tyrosine kinase inhibitor based therapy.
The spleen tyrosine kinase Syk is an enigmatic protein tyrosine kinase functional in a number of diverse cellular processes. It is best known as a non receptor protein tyrosine kinase involved in signal transduction in cells of hematopoietic origin and plays a crucial role in signaling in most of these cells. It is involved in B and T-cell function, platelet aggregation, mast cell signaling, neutrophils and macrophages. Recently it has been found in tissues outside of the hematopoietic lineage. Perhaps the most interesting non-traditional role of Syk is that of a potential tumor suppressor in breast cancer. Absence of Syk protein in primary breast tumors is correlated with poor outcomes. Syk deficient cells have increased motility which is restored to normalcy by replacement with wild-type Syk. Syk also associates with the actin and tubulin cytoskeleton and is an alpha-tubulin kinase. The central role that Syk has in a number of cellular processes makes it an ideal starting point for broad therapeutic targeting.
Navara
Christopher S
CS
Dept. of Obstetrics, Gynecology and Reprod. Sci. and Pittsburgh Development Center University of Pittsburgh 204 Craft Avenue Pittsburgh, PA 15213, USA. cnavara@pdc.magee.edu
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072377:Syk Kinase
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase