Apoptosis-associated tyrosine kinase and neuronal cell death.

Neurochemical Research
Jane P HughesStephen D Skaper

Abstract

Apoptosis-associated tyrosine kinase (AATYK) is up-regulated by phosphorylation in cultured cerebellar granule neurons (CGN) undergoing apoptosis upon switch to low KCl-containing medium. However, the underlying signaling pathways remain to be fully characterized. When CGN at culture day 7 were switched from 25 mM KCl (K25) to 5 mM (K5) medium, AATYK band migration on SDS-PAGE shifted to a more slowly migrating position expected for the hyperphosphorylated protein. The apoptosis-inducing agent C(2)-ceramide also caused a mobility shift of the AATYK protein. Exposing CGN (K25) to L-type voltage-dependent Ca(2+) channel antagonists shifted the AATYK band to the K5-induced position, while the Ca(2+) channel activator FPL-64176 had the contrary effect. FK-506, a calcineurin inhibitor caused AATYK hyperphosphorylation under high KCl conditions. CGN death in K5 medium is linked to inhibition of the PI 3-kinase/Akt survival pathway and concomitant activation of the pro-apoptotic downstream target glycogen synthase kinase-3 (GSK-3). GSK-3 inhibitors blocked the K5-induced mobility shift of AATYK. Moreover, CGN cultured from AATYK-deficient mice remained sensitive to death in K5 medium. Thus, AATYK activation may not be a physiologicall...Continue Reading

References

Mar 1, 1990·Journal of Neurochemistry·J PatelA Salama
Mar 1, 1986·Brain Research·M ManthorpeS Varon
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·S R D'MelloP Calissano
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·P S Klein, D A Melton
Jun 5, 1998·The Journal of Biological Chemistry·C B KleeX Wang
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P LambertW L Klein
Aug 1, 1998·The Journal of Biological Chemistry·M Pap, G M Cooper
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·A A GenazzaniD Guerini
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·E Chalecka-Franaszek, D M Chuang
Dec 3, 1999·Journal of Neurochemistry·P YuanH K Manji
Jun 22, 2000·The Journal of Biological Chemistry·T HergetG van Echten-Deckert
Sep 22, 2000·The Biochemical Journal·S P DaviesP Cohen
Nov 30, 2000·Molecular and Cellular Biology·M LiK A Heidenreich
Jan 9, 2001·Brain Research. Molecular Brain Research·M ShojiH Okazawa
May 30, 2001·Trends in Molecular Medicine·T E Golde, S G Younkin
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·M J BerridgeM D Bootman
Jun 12, 2002·The Journal of Biological Chemistry·Karie N DahlgrenMary Jo LaDu
Oct 24, 2002·The Journal of Biological Chemistry·Hong Wang, David L Brautigan
Nov 8, 2002·Journal of Neurochemistry·Charles HarrisEugene M Johnson
Apr 1, 2003·Molecular and Cellular Biology·Alain Lilienbaum, Alain Israël
Mar 10, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Seiji KawaTadashi Yamamoto
May 8, 2004·Molecular and Cellular Endocrinology·C L ChikA K Ho
Aug 31, 2004·Drug News & Perspectives·Taisuke Tomita, Takeshi Iwatsubo

❮ Previous
Next ❯

Citations

Sep 17, 2015·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Ming TongSuzanne M de la Monte
Jun 21, 2011·Neurochemistry International·Aurelio Vazquez de la TorreEster Verdaguer
Oct 18, 2012·Physiological Reviews·Kenneth B Gagnon, Eric Delpire
Jul 28, 2020·Frontiers in Molecular Neuroscience·Shin-Ichi HisanagaMineko Tomomura

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.