Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 17 February 2009
Vol. 2, Issue 58, p. ra6
[DOI: 10.1126/scisignal.2000021]

RESEARCH ARTICLES

Editor's Summary

Is Timing Everything?
Five tyrosine residues in the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1) undergo autophosphorylation, a process that both enhances its kinase activity and provides binding sites for downstream signaling molecules. Lew et al. investigated the mechanisms underlying this sequential and precisely ordered autophosphorylation and determined that it was under kinetic control, with the order of phosphorylation depending on the location of individual tyrosines within the primary and tertiary structures of the FGFR1 kinase domain. Intriguingly, the order in which these tyrosine residues underwent autophosphorylation was disrupted by a glioblastoma-derived, oncogenic FGFR1 point mutation. The authors postulate that such mutations may also alter the temporal recruitment of downstream signaling molecules and this may contribute to their oncogenic activity.

Citation: E. D. Lew, C. M. Furdui, K. S. Anderson, J. Schlessinger, The Precise Sequence of FGF Receptor Autophosphorylation Is Kinetically Driven and Is Disrupted by Oncogenic Mutations. Sci. Signal. 2, ra6 (2009).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers.
Y. Opatowsky, I. Lax, F. Tome, F. Bleichert, V. M. Unger, and J. Schlessinger (2014)
PNAS 111, 1772-1777
   Abstract »    Full Text »    PDF »
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly.
N. Simonis, I. Migeotte, N. Lambert, C. Perazzolo, D. C. de Silva, B. Dimitrov, C. Heinrichs, S. Janssens, B. Kerr, G. Mortier, et al. (2013)
J. Med. Genet. 50, 585-592
   Abstract »    Full Text »    PDF »
ERK-Mediated Phosphorylation of Fibroblast Growth Factor Receptor 1 on Ser777 Inhibits Signaling.
M. Zakrzewska, E. M. Haugsten, B. Nadratowska-Wesolowska, A. Oppelt, B. Hausott, Y. Jin, J. Otlewski, J. Wesche, and A. Wiedlocha (2013)
Science Signaling 6, ra11
   Abstract »    Full Text »    PDF »
Grb2, a Double-Edged Sword of Receptor Tyrosine Kinase Signaling.
A. A. Belov and M. Mohammadi (2012)
Science Signaling 5, pe49
   Abstract »    Full Text »    PDF »
Macrophage Proliferation Is Regulated through CSF-1 Receptor Tyrosines 544, 559, and 807.
W. Yu, J. Chen, Y. Xiong, F. J. Pixley, Y.-G. Yeung, and E. R. Stanley (2012)
J. Biol. Chem. 287, 13694-13704
   Abstract »    Full Text »    PDF »
Distinct Involvement of the Gab1 and Grb2 Adaptor Proteins in Signal Transduction by the Related Receptor Tyrosine Kinases RON and MET.
A. Chaudhuri, M.-H. Xie, B. Yang, K. Mahapatra, J. Liu, S. Marsters, S. Bodepudi, and A. Ashkenazi (2011)
J. Biol. Chem. 286, 32762-32774
   Abstract »    Full Text »    PDF »
A Novel Mode of Protein Kinase Inhibition Exploiting Hydrophobic Motifs of Autoinhibited Kinases: DISCOVERY OF ATP-INDEPENDENT INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR.
S. Eathiraj, R. Palma, M. Hirschi, E. Volckova, E. Nakuci, J. Castro, C.-R. Chen, T. C. K. Chan, D. S. France, and M. A. Ashwell (2011)
J. Biol. Chem. 286, 20677-20687
   Abstract »    Full Text »    PDF »
A regression framework incorporating quantitative and negative interaction data improves quantitative prediction of PDZ domain-peptide interaction from primary sequence.
X. Shao, C. S. H. Tan, C. Voss, S. S. C. Li, N. Deng, and G. D. Bader (2011)
Bioinformatics 27, 383-390
   Abstract »    Full Text »    PDF »
Roles of Fibroblast Growth Factor Receptors in Carcinogenesis.
E. M. Haugsten, A. Wiedlocha, S. Olsnes, and J. Wesche (2010)
Mol. Cancer Res. 8, 1439-1452
   Abstract »    Full Text »    PDF »
Computational Tools for the Interactive Exploration of Proteomic and Structural Data.
J. H. Morris, E. C. Meng, and T. E. Ferrin (2010)
Mol. Cell. Proteomics 9, 1703-1715
   Abstract »    Full Text »    PDF »
Mammary Gland Growth Factors: Roles in Normal Development and in Cancer.
N. E. Hynes and C. J. Watson (2010)
Cold Spring Harb Perspect Biol 2, a003186
   Abstract »    Full Text »    PDF »
Signal Transducers and Activators of Transcription-3 Binding to the Fibroblast Growth Factor Receptor Is Activated by Receptor Amplification.
A. A. Dudka, S. M. M. Sweet, and J. K. Heath (2010)
Cancer Res. 70, 3391-3401
   Abstract »    Full Text »    PDF »
Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells.
J. H. Bae, T. J. Boggon, F. Tome, V. Mandiyan, I. Lax, and J. Schlessinger (2010)
PNAS 107, 2866-2871
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 03 March 2009.
J. Schlessinger and A. M. VanHook (2009)
Science Signaling 2, pc5
   Abstract »    Full Text »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882