Phosphoinositide 3-kinase γ participates in T cell receptor-induced T cell activation

被引:84
作者
Alcázar, Isabela
Marqués, Miriam
Kumar, Amit
Hirsch, Emilio
Wymann, Matthias
Carrera, Ana C.
Barber, Domingo F. [1 ]
机构
[1] Consejo Sup Invest Cien, Ctr Nacl Biotecnol, Dept Immunol & Oncol, Madrid 28049, Spain
[2] Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, I-10126 Turin, Italy
[3] Univ Basel, Inst Biochem & Genet, Dept Clin & Biol Sci, CH-4058 Basel, Switzerland
关键词
D O I
10.1084/jem.20070366
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Class I phosphoinositide 3 - kinases (P13Ks) constitute a family of enzymes that generates 3-phosphorylated polyphosphoinositides at the cell membrane after stimulation of protein tyrosine (Tyr) kinase - associated receptors or G protein - coupled receptors (GPCRs). The class I P13Ks are divided into two types: class I-A p85/p110 heterodimers, which are activated by Tyr kinases, and the class I-B p110 gamma isoform, which is activated by GPCR. Although the T cell receptor (TCR) is a protein Tyr kinase - associated receptor, p110 gamma deletion affects TCR-induced T cell stimulation. We examined whether the TCR activates p110 gamma, as well as the consequences of interfering with p110 gamma expression or function for T cell activation. We found that after TCR ligation, p110 gamma interacts with G alpha(q/11), lymphocyte-specific Tyr kinase, and zeta-associated protein. TCR stimulation activates p110 gamma, which affects 3-phosphorylated polyphosphoinositide levels at the immunological synapse. We show that TCR-stimulated p110 gamma controls RAS-related C3 botulinum substrate 1 activity, F-actin polarization, and the interaction between T cells and antigen-presenting cells, illustrating a crucial role for p110 gamma in TCR-induced T cell activation.
引用
收藏
页码:2977 / 2987
页数:11
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