SYK
小结
SYK编码蛋白是一种细胞质酪氨酸激酶，通过将其SH2结构域与膜受体的结合而被募集到细胞膜，随后通过磷酸化活化。SYK主要在造血细胞中表达，SYK介导的信号通路的激活是B细胞和淋巴系统发育所必需的。SYK的活性用来激活介导细胞粘附、破骨细胞成熟、血小板活化和血管发育的各种其他信号通路。SYK的体细胞突变在人类癌症中罕见发生，然而，激活的SYK信号已在白血病和淋巴瘤中被发现。此外，SYK信号的激活被描述为卵巢癌化疗耐药的机制。
SYK encodes a tyrosine kinase involved in signal transduction. Upregulation of SYK is found in lymphomas, leukemias and select epithelial tumors.SYK is a cytoplasmic tyrosine kinase that is recruited to the cell membrane through binding of its SH2 domain to membrane receptors and is subsequently activated via phosphorylation. SYK is predominantly expressed in hematopoietic cells and activation of SYK-mediated signaling pathways is necessary for B-cell and lymphatic system development. In B- and T-cell signal transduction, SYK binds ITAM adaptor molecules that complex with the B-cell receptor (BCR) and T-cell receptor (TCR) mediating critical immune regulatory pathways. SYK activity is required to activate various other signaling pathways that mediate cellular adhesion, osteoclast maturation, platelet activation and vascular development. Somatic mutations in SYK are rare in human cancers; however, activated SYK signaling has been identified in leukemias and lymphomas. In addition, activation of SYK signaling has been described as a mechanism of ovarian cancer chemoresistance. Case reports have reported translocations in SYK in myelodysplastic syndromes (MDS) and lymphomas. The SYK tyrosine kinase inhibitor fostamatinib is currently being evaluated in clinical trials for efficacy in hematopoietic malignancies.