Korade-Mirnics Z, Corey S J
Department of Pediatrics and Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
J Leukoc Biol. 2000 Nov;68(5):603-13.
A concert of antigens, antibodies, cytokines, adhesion molecules, lipid factors, and their different receptors mediate leukocyte development and inflammatory responses. Regardless of the stimulus and receptor type, members of the Src family of protein tyrosine kinases (PTKs) play a critical role in initiating the numerous intracellular signaling pathways. Recruited and activated by the receptor, these Src PTKs amplify and diversify the signal. Multiple pathways arise, which affect cell migration, adhesion, phagocytosis, cell cycle, and cell survival. Essential nonredundant properties of Src PTKs have been identified through the use of gene targeting in mice or in the somatic cell line DT40. Because of their role in mediating leukocyte proliferation and activation, Src PTKs serve as excellent drug targets. Inhibitors of Src family members and dependent pathways may be useful in the treatment of human diseases similar to drugs known to inhibit other signal transduction pathways.
抗原、抗体、细胞因子、黏附分子、脂质因子及其不同受体协同作用,介导白细胞发育和炎症反应。无论刺激因素和受体类型如何,蛋白酪氨酸激酶(PTK)的Src家族成员在启动众多细胞内信号通路中都起着关键作用。这些Src PTK被受体招募并激活后,会放大信号并使其多样化。由此产生多种信号通路,影响细胞迁移、黏附、吞噬作用、细胞周期和细胞存活。通过在小鼠或体细胞系DT40中使用基因靶向技术,已确定了Src PTK的重要且不可替代的特性。由于其在介导白细胞增殖和激活中的作用,Src PTK是极佳的药物靶点。与已知抑制其他信号转导通路的药物类似,Src家族成员及其相关信号通路的抑制剂可能对人类疾病的治疗有用。