| Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction |
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| Author(s): Furdui CM, Lew ED, Schlessinger J, Anderson KS |
| Source: MOLECULAR CELL Volume: 21 Issue: 5 Pages: 711-717 Published: MAR 3 2006 |
| Times Cited: 36 References: 29 |
| Abstract: Tyrosine phosphorylation of cellular proteins induced by extracellular cues serves as a critical mediator in the control of a great variety of cellular processes. Here, we describe an integrated experimental approach including rapid quench methodology and ESI-LC-MS/MS as well as time-resolved ESI-MS to demonstrate that tyrosine autophosphorylation of the catalytic tyrosine kinase domain of FGF-receptor-1 (FGFR1) is mediated by a sequential and precisely ordered reaction. We also demonstrate that the rate of catalysis of two FGFR substrates is enhanced by 50- to 100-fold after autophosphorylation of Y653 in the activation loop, whereas autophosphorylation of the second site in the activation loop (Y654) results in 500- to 1000-fold increase in the rate of substrate phosphorylation. We propose that FGFR1 is activated by a two-step mechanism mediated by strictly ordered and regulated autophosphorylation, suggesting that distinct phosphorylation states may provide both temporal and spatial resolution to receptor signaling. |
| Document Type: Article |
| Language: English |
| Reprint Address: Schlessinger, J (reprint author), Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA |
Addresses:
1. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 023OB |
| ISSN: 1097-2765 |
| DOI: 10.1016/j.molcel.2006.01.022 |