Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction

Molecular Cell
Cristina M FurduiKaren S Anderson

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 1,000-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.

References

Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A M HoneggerJ Schlessinger
Nov 1, 2000·Cell·J Schlessinger
May 18, 2001·Nature·P Blume-Jensen, T Hunter
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y R HadariJ Schlessinger
Nov 1, 2001·The Journal of Biological Chemistry·Hanno SteenMatthias Mann
Nov 6, 2001·Nature Structural Biology·S FavelyukisW T Miller
Feb 26, 2003·Molecular & Cellular Proteomics : MCP·Anders M HinsbyMatthias Mann
Aug 14, 2003·Journal of the American Chemical Society·Zhili LiKaren S Anderson
Aug 18, 2004·Nature Biotechnology·Blagoy BlagoevMatthias Mann
Sep 2, 2004·Nature Biotechnology·Sam A Johnson, Tony Hunter
May 3, 2005·Cytokine & Growth Factor Reviews·V P EswarakumarJ Schlessinger
May 3, 2005·Cytokine & Growth Factor Reviews·Richard Grose, Clive Dickson

❮ Previous
Next ❯

Citations

Nov 17, 2007·Journal of Mathematical Biology·Liming Wang, Eduardo D Sontag
Apr 6, 2012·Annals of Biomedical Engineering·Sameer S Bajikar, Kevin A Janes
Oct 24, 2013·The International Journal of Biochemistry & Cell Biology·Abbie E FearonRichard P Grose
Feb 4, 2010·Journal of Medicinal Chemistry·Krishna P RavindranathanWilliam L Jorgensen
Sep 29, 2007·Nature Methods·Eric S WitzeNatalie G Ahn
Feb 14, 2013·Nature Reviews. Molecular Cell Biology·Regina Goetz, Moosa Mohammadi
Dec 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Huaibin ChenMoosa Mohammadi
Nov 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jonathan R St-GermainMichael F Moran
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jae Hyun BaeJoseph Schlessinger
Jun 12, 2010·The Journal of Biological Chemistry·Roland ScholzDietbert Neumann
Aug 19, 2011·Molecular Biology of the Cell·Stacy L HarveyDouglas R Kellogg
Jul 24, 2008·Journal of the Royal Society, Interface·Aneil MallavarapuJeremy Gunawardena
Jun 5, 2013·Cold Spring Harbor Perspectives in Biology·Artur A Belov, Moosa Mohammadi
Feb 14, 2013·Science Signaling·Malgorzata ZakrzewskaAntoni Wiedlocha
Nov 11, 2011·Science Translational Medicine·Scott C BreslerYaël P Mossé
Oct 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stephen C Pratt, David J T Sumpter
Apr 8, 2014·Cellular and Molecular Life Sciences : CMLS·Leo K IwaiPaul H Huang
May 10, 2013·Analytical and Bioanalytical Chemistry·Sang Kwang LeeYoung Mok Park
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Fumin ShiMark A Lemmon
Jan 22, 2013·The Journal of Biological Chemistry·Hsueh-Liang FuRafael Fridman
Apr 23, 2008·Neurochemical Research·Stine Maria HansenVladimir Berezin
Oct 14, 2014·Expert Opinion on Therapeutic Targets·Anselmo PapaFederica Tomao
Dec 30, 2009·The Journal of Cell Biology·Chiara FrancavillaUgo Cavallaro
Sep 16, 2014·Journal of Molecular Biology·E LescaM Augustin
Feb 13, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yoshihiro KobashigawaFuyuhiko Inagaki
May 5, 2011·Critical Reviews in Biochemistry and Molecular Biology·Jonathan P DiNitto, Joe C Wu
Oct 31, 2009·Pharmacology & Therapeutics·Victoria Knights, Simon J Cook
Oct 15, 2014·Proteomics·Jonathan R St-GermainMichael F Moran

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.