Signaling initiated by overexpression of the fibroblast growth factor receptor-1 investigated by mass spectrometry
Research output: Contribution to journal › Journal article › Research › peer-review
Overexpression of the fibroblast growth factor receptor-1 (FGFR-1), a prototypic receptor tyrosine kinase, is a feature of several human tumors. In human 293 cells overexpression of the FGFR-1 leads to constitutive activation of the receptor with concomitant sustained high increase in the cellular level of phosphotyrosine-containing proteins. Here we use mass spectrometry to study the tyrosine-phosphorylated proteins induced by overexpression of the FGFR-1. Several well known components of FGFR-1 signaling were identified along with two novel candidates: NS-1-associated protein-1 and target of Myb 1-like protein. We subsequently applied mass spectrometry precursor ion scanning to identify 22 tyrosine phosphorylation sites distributed on six substrate proteins of the FGFR-1 or downstream tyrosine kinases. Novel in vivo tyrosine phosphorylation sites were found in the FGFR-1, phospholipase Cgamma, p90 ribosomal S6 kinase, cortactin, and NS-1-associated protein-1 as a result of sustained FGFR-1 signaling, and we propose these as functional links to downstream molecular and cellular processes.
Original language | English |
---|---|
Journal | Molecular and Cellular Proteomics |
Volume | 2 |
Issue number | 1 |
Pages (from-to) | 29-36 |
Number of pages | 7 |
ISSN | 1535-9476 |
DOIs | |
Publication status | Published - 2003 |
Externally published | Yes |
Bibliographical note
Keywords: Blotting, Western; Cell Line; Cortactin; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Heterogeneous-Nuclear Ribonucleoproteins; Humans; Mass Spectrometry; Microfilament Proteins; Phosphorylation; Precipitin Tests; Protein Binding; Proteins; RNA-Binding Proteins; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Fibroblast Growth Factor; Ribosomal Protein S6 Kinases, 90-kDa; Signal Transduction; Transfection; Tyrosine
ID: 16275892