炎症与癌症中的PI3K药物靶点

PI3Ks-drug targets in inflammation and cancer.

作者信息

Wymann Matthias

机构信息

Institute Biochemistry & Genetics, Department Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland,

出版信息

Subcell Biochem. 2012;58:111-81. doi: 10.1007/978-94-007-3012-0_5.

DOI:10.1007/978-94-007-3012-0_5

PMID:22403076

Abstract

Phosphoinositide 3-kinases (PI3Ks) control cell growth, proliferation, cell survival, metabolic activity, vesicular trafficking, degranulation, and migration. Through these processes, PI3Ks modulate vital physiology. When over-activated in disease, PI3K promotes tumor growth, angiogenesis, metastasis or excessive immune cell activation in inflammation, allergy and autoimmunity. This chapter will introduce molecular activation and signaling of PI3Ks, and connections to target of rapamycin (TOR) and PI3K-related protein kinases (PIKKs). The focus will be on class I PI3Ks, and extend into current developments to exploit mechanistic knowledge for therapy.

摘要

磷酸肌醇3激酶（PI3Ks）控制细胞生长、增殖、细胞存活、代谢活性、囊泡运输、脱颗粒和迁移。通过这些过程，PI3Ks调节重要的生理功能。当在疾病中过度激活时，PI3K促进肿瘤生长、血管生成、转移，或在炎症、过敏和自身免疫中导致免疫细胞过度激活。本章将介绍PI3Ks的分子激活和信号传导，以及与雷帕霉素靶蛋白（TOR）和PI3K相关蛋白激酶（PIKKs）的联系。重点将放在I类PI3Ks上，并延伸到利用机制知识进行治疗的当前进展。