Phosphatidylinositol 3‐kinase is recruited to a specific site in the activated IL‐1 receptor I

FEBS Letters

Tsukada, Junichi⁴  Auron, Philip E⁴  Marmiroli, Sandra⁵  Ferri, Alberto⁶  Bavelloni, Alberto¹  Ruzzene, Maria²  Cenni, Vittoria⁵  Faenza, Irene⁵  Koyama, Yoshinobu⁴  Ognibene, Andrea¹  Toker, Alex³  Maraldi, Nadir M⁵  Sirri, Alessandra¹ 

[1] Laboratorio Biologia Cellulare I.O.R., Bologna, Italy;Department of Biochemistry, University of Padova, Padova, Italy;Boston Biomedical Research Institute, Boston, MA, USA;Department of Pathology, Harvard Medical School, Boston, MA, USA;Istituto di Citomorfologia Normale e Patologica del C.N.R., via di Barbiano 1/10, 40136 Bologna, Italy;Department of Biochemistry, University of Ferrara, Ferrara, Italy

关键词: Phosphatidylinositol 3-kinase;    Interleukin-1 receptor;    Nuclear factor κB;    Human osteosarcoma cell line;    IL-1;    interleukin 1;    IL-1RI;    IL-1 receptor I;    IL-1R-AcP;    IL-1 receptor accessory protein;    NF-κB;    nuclear factor κB;    TNF;    tumour necrosis factor;    TRAF;    TNF receptor associated factor;    IRAK;    IL-1 receptor associated kinase;    PI 3-kinase;    phosphatidylinositol 3-kinase;    CAT;    chloramphenicol acetyltransferase;    NIK;    NF-κB inducing kinase;   

DOI  :  10.1016/S0014-5793(98)01270-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interleukin 1 (IL-1) delivers a stimulatory signal which increases the expression of a set of genes by modulating the transcription factor NF-κB. The IL-1 receptors are transmembrane glycoproteins which lack a catalytic domain. The C-terminal portion of the type I IL-1 receptor (IL-1RI) is essential for IL-1 signalling and for IL-1 dependent activation of NF-κB. This portion contains a putative phosphatidylinositol 3-kinase (PI 3-kinase) binding domain (Tyr-E-X-Met), which is highly conserved between the human, mouse and chicken sequences, as well as the related cytoplasmic domain of the Drosophila receptor Toll. This observation prompted us to investigate the role of PI 3-kinase in IL-1 signalling. Here we report evidence that PI 3-kinase is recruited by the activated IL-1RI, causing rapid and transient activation of PI 3-kinase. We also show that the receptor is tyrosine phosphorylated in response to IL-1. Expression of a receptor mutant lacking the putative binding site for p85 demonstrates that Tyr⁴⁷⁹ in the receptor cytoplasmic domain is essential for PI 3-kinase activation by IL-1. Our results indicate that PI 3-kinase is likely to be an important mediator of some IL-1 effects, providing docking sites for additional signalling molecules.

【 授权许可】

Unknown