Sotsios Y, Ward S G
Department of Pharmacy and Pharmacology, Bath University, Avon, UK.
Immunol Rev. 2000 Oct;177:217-35. doi: 10.1034/j.1600-065x.2000.17712.x.
Chemokines can couple to distinct signalling pathways that have been demonstrated to mediate not only migration, but also cell growth and transcriptional activation. One particular signalling pathway, namely that controlled by the lipid kinase phosphoinositide 3-kinase (PI3K), has been the focus of much attention with respect to its activation by chemokine receptors and the role it plays in regulating cell migration. Identification of PI3K is arguably one of the most exciting recent developments in biochemical signalling. Pharmacological and genetic studies have now convincingly shown that both CC and CXC chemokines stimulate PI3K-dependent chemotaxis of inflammatory cells such as eosinophils, macrophages, neutrophils and T lymphocytes. This review considers the role of specific sub-classes of PI3Ks (e.g. the p85/p110 heterodimer, PI3Kgamma and PI3K-C2alpha) as well as their downstream effector targets in mediating chemokine-stimulated cell migration.
趋化因子可与不同的信号通路偶联，这些信号通路不仅能介导细胞迁移，还能介导细胞生长和转录激活。其中一条特定的信号通路，即由脂质激酶磷酸肌醇3激酶（PI3K）控制的信号通路，因其被趋化因子受体激活以及在调节细胞迁移中所起的作用而备受关注。PI3K的发现可以说是生化信号领域最近最令人兴奋的进展之一。药理学和遗传学研究现已令人信服地表明，CC趋化因子和CXC趋化因子均可刺激嗜酸性粒细胞、巨噬细胞、中性粒细胞和T淋巴细胞等炎症细胞的PI3K依赖性趋化作用。本文综述了PI3K特定亚类（如p85/p110异二聚体、PI3Kγ和PI3K-C2α）及其下游效应靶点在介导趋化因子刺激的细胞迁移中的作用。
