a conserved motif in the itk ph-domain is required for phosphoinositide binding and tcr signaling but dispensable for adaptor protein interactions的守恒的主题itk ph-domain磷酸肌醇需要绑定和细胞信号但可有可无的适配器蛋白质相互作用.pdfVIP

A Conserved Motif in the ITK PH-Domain Is Required for Phosphoinositide Binding and TCR Signaling but Dispensable for Adaptor Protein Interactions 1. 1. 2 1 3 Nupura Hirve , Roman M. Levytskyy , Stephanie Rigaud , David M. Guimond , Tomasz Zal , 2 1 Karsten Sauer , Constantine D. Tsoukas * 1 Molecular Biology Institute and Center for Microbial Sciences, Department of Biology, San Diego State University, San Diego, California, United States of America, 2 Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America, 3 MD Anderson Cancer Center, Department of Immunology, The University of Texas, Houston, Texas, United States of America Abstract Binding of the membrane phospholipid phosphatidylinositol 3,4,5-trisphosphate (PIP ) to the Pleckstrin Homology (PH) 3 domain of the Tec family protein tyrosine kinase, Inducible T cell Kinase (ITK), is critical for the recruitment of the kinase to the plasma membrane and its co-localization with the TCR-CD3 molecular complex. Three aromatic residues, termed the FYF motif, located in the inner walls of the phospholipid-binding pocket of the ITK PH domain, are conserved in the PH domains of all Tec kinases, but not in other PH-domain containing proteins, suggesting an important function of the FYF motif in the Tec kinase family. However, the biological significance of the FYF amino acid motif in the ITK-PH domain is unknown. To elucidate it, we have tested the effects of a FYF triple mutant (F26S, Y90F, F92S), hence