Kinetics of trkA tyrosine kinase activity and inhibition by K-252a

Archives of Biochemistry and Biophysics
T S AngelesC A Dionne

Abstract

The kinetic mechanism of the trk receptor-linked tyrosine kinase was determined using a baculovirus expressed trk kinase domain and a bacterially expressed phospholipase C-gamma/glutathione S-transferase (PLC-gamma/ GST) fusion protein as substrate. Product and dead-end inhibition studies indicate an ordered association of substrates to trkA kinase with the nucleotide ATP binding prior to the exogenous substrate PLC-gamma/GST, followed by release of the phosphorylated PLC-gamma/GST product prior to release of ADP (sequential ordered bi-bi mechanism). This is in contrast to the reported kinetic mechanisms of closely related EGF receptor and insulin receptor kinases which appear to proceed via a rapid equilibrium random mechanism. The indolocarbazole K-252a, which was previously shown to be a potent and relatively selective inhibitor of trk kinase activity, acts as a competitive inhibitor with respect to ATP. The data suggest that potent and selective kinase inhibitors can be rationally designed by exploring subtle variations surrounding the nucleotide binding sites of receptor tyrosine kinases.

References

Nov 15, 1979·Analytical Biochemistry·P A LanzettaO A Candia
Jan 1, 1992·Cold Spring Harbor Symposia on Quantitative Biology·J SchlessingerA Ullrich
Nov 1, 1992·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A Levitzki
Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M L VetterD R Kaplan
Jan 25, 1991·Cell·L C CantleyS Soltoff
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M F MoranT Pawson
Aug 31, 1990·Biochemical and Biophysical Research Communications·L H ElliottJ S Nixon
Mar 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M I WahlG Carpenter
Jun 1, 1989·Trends in Pharmacological Sciences·U T Rüegg, G M Burgess
Jan 1, 1989·Molecular and Cellular Biology·D Martin-ZancaM Barbacid
Aug 1, 1986·The Journal of Antibiotics·H KaseY Matsuda
Jan 1, 1984·Advances in Enzyme Regulation·A R Goldberg, T W Wong
Jul 1, 1995·The Journal of Antibiotics·S OmuraH Takeshima
Dec 1, 1994·The European Journal of Neuroscience·G R LewinL M Mendell
Jan 1, 1993·Annual Review of Biochemistry·S RaffioniS E Buxser
Apr 5, 1996·Analytical Biochemistry·T S AngelesC A Dionne
May 2, 1997·The Journal of Biological Chemistry·P R YoungJ C Lee
Aug 7, 1997·International Journal of Cancer. Journal International Du Cancer·A M CamorattoC A Dionne

❮ Previous
Next ❯

Citations

Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·H MorenoR Llinás
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Leo H WangEugene M Johnson
Nov 1, 2005·Expert Opinion on Investigational Drugs·Guang-Yi Zhang, Quan-Guang Zhang
Oct 29, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Avraham BeigelmanRachel Levy
Apr 6, 2007·International Journal of Experimental Pathology·Matthew E HandleyDavid R Katz
Nov 22, 2005·Biochemical and Biophysical Research Communications·Atsuko KiyamaKatsuya Nagai
Mar 12, 2004·Bioorganic & Medicinal Chemistry Letters·Edgar R WoodKaren Lackey
Sep 14, 2018·Archives of Dermatological Research·Min ZhangYongqian Cao
Oct 22, 2002·The Journal of Biological Chemistry·Philippe P RouxPhilip A Barker

❮ 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.