A Tyrosine-Phosphorylated Carboxy-Terminal Peptide of the Fibroblast Growth Factor Receptor (Flg) Is a Binding Site for the SH2 Domain of Phospholipase C-γ1

作者：M. Mohammadi, Annemarie Honegger, D. Rotin, René W. Fischer, Francoise Bellot, W Li, Craig A. Dionne, Michael Jaye, Morton E. Rubinstein, Joseph Schlessinger · 发表于：Molecular and Cellular Biology · 年份：1991 · DOI：10.1128/mcb.11.10.5068-5078.1991 · 被引用次数：100 · 研究领域：Fibroblast Growth Factor Research、Protein Kinase Regulation and GTPase Signaling、Proteoglycans and glycosaminoglycans research

Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR; encoded by the flg gene) and other receptors with tyrosine kinase activity. It has been demonstrated that the src homology region 2 (SH2 domain) of PLC-gamma and of other signalling molecules such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85 direct their binding toward tyrosine-autophosphorylated regions of the epidermal growth factor or platelet-derived growth factor receptor. In this report, we describe the identification of Tyr-766 as an autophosphorylation site of flg-encoded FGFR by direct sequencing of a tyrosine-phosphorylated tryptic peptide isolated from the cytoplasmic domain of FGFR expressed in Escherichia coli. The same phosphopeptide was found in wild-type FGFR phosphorylated either in vitro or in living cells. Like other growth factor receptors, tyrosine-phosphorylated wild-type FGFR or its cytoplasmic domain becomes associated with intact PLC-gamma or with a fusion protein containing the SH2 domain of PLC-gamma. To delineate the site of association, we have examined the capacity of a 28-amino-acid tryptic peptide containing phosphorylated Tyr-766 to bind to various constructs containing SH2 and other domains of PLC-gamma. It is demonstrated that the tyrosine-phosphorylated peptide binds specifically to the SH2 domain but not to the SH3 domain or other regions of PLC-gamma. Hence, Tyr-766 and its flanking sequences represent a major ...