Abstract
Src is a non-receptor protein tyrosine kinase that transduces signals regulating cell growth and differentiation. We report here that activation of signaling pathway after blockade of tyrosine phosphorylation by PP2 (4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a potent and selective inhibitor of the Src-family tyrosine kinase, can lead to cell death in murine B cell leukemia, 70Z/3. Death from PP2 occurred by apoptosis as indicated by the induction of caspase activation and annexin V/propidium iodide staining. Interestingly, PP2 was found to be able to enhance the DNA binding activity of nuclear factor kappaB (NF-kappaB) before induction of apoptosis without accompanying by increased phosphorylation of inhibitor of NF-kappaB-alpha (IkappaB-alpha). Additionally, immunoblotting analysis with PP2-treated cell extract demonstrated that, compared to other protein kinase C (PKC) isotypes, the translocation of novel PKC isotypes from the cytosol to membrane fraction was sustained for a longer time. These data suggest that the inhibition of Src-mediated tyrosine phosphorylation by PP2 may tilt the balance between each PKC isotypes, which in turn, activate NF-kappaB transcription factor, leading to apoptosis.
References
Oct 23, 1992·Science·Y Nishizuka
Dec 26, 1986·Cell·R Sen, D Baltimore
Jun 20, 1994·FEBS Letters·M GschwendtF Marks
Jun 1, 1995·Current Opinion in Immunology·J H Russell
Sep 1, 1994·Molecular and Cellular Biology·Q Li, J A Stamatoyannopoulos
Jan 12, 1996·The Journal of Biological Chemistry·J H HankeP A Connelly
Oct 1, 1995·Molecular Biology of the Cell·D Bray, R B Bourret
Mar 8, 1996·The Journal of Biological Chemistry·M F DenningS H Yuspa
Jan 10, 1997·The Journal of Biological Chemistry·A DembinskyS Ravid
Aug 15, 1997·The Biochemical Journal·G M Cohen
Nov 5, 1997·Science·J D WoroniczD V Goeddel
May 15, 1998·Oncogene·M ShanmugamM Hunzicker-Dunn
Oct 3, 1998·The Journal of Biological Chemistry·X Feng, Y A Hannun
Oct 21, 1998·Oncogene·P L Schwartzberg
Jun 25, 1999·Cell Death and Differentiation·B LinR I Scheinman
Jun 26, 1999·The Journal of Biological Chemistry·M E ReylandD O Quissell
Aug 7, 1999·The Journal of Biological Chemistry·S A TrushinC V Paya
Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Feb 17, 2000·The EMBO Journal·D B ParekhP J Parker
Jun 22, 2000·Cancer·T H WangY K Soong
Aug 5, 2000·Cell Death and Differentiation·D JohnsonJ Wyke
Aug 18, 2000·The Journal of Biological Chemistry·M TakahashiY Ono
Aug 25, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·E C DempseyR O Messing
Dec 15, 2000·Oncogene·J D BjorgeD J Fujita
Jan 10, 2001·Development, Growth & Differentiation·K SatoY Fukami
Feb 13, 2001·Molecular Pharmacology·M Lee, Y J Jeon
Feb 13, 2001·Molecular Pharmacology·K K MannS Quadri
Mar 20, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·Q Chang, B L Tepperman
Sep 5, 2001·Molecular and Cellular Biology·D KrappmannC Scheidereit
Dec 26, 2001·Chemical Reviews·A C Newton
Citations
May 22, 2008·Breast Cancer Research and Treatment·S HiscoxR I Nicholson
Oct 19, 2011·Neurotoxicity Research·Tsuneo TakaderaSatoru Kato
Nov 26, 2010·Acta Pharmacologica Sinica·Yan ZHULin CAO
Feb 23, 2012·Carcinogenesis·Ryoji EguchiYoshihiro Fujimori
Dec 17, 2008·Hematology·Susan O'Brien
May 23, 2012·Expert Opinion on Investigational Drugs·Tadeusz Robak, Ewa Robak
Jun 15, 2010·FEBS Letters·Xiang LiuLiying Du
Dec 27, 2011·Experimental Cell Research·Christoffer TammCecilia Annerén
Jan 17, 2007·Journal of Hepatology·Enrico N De ToniSören T Eichhorst
Jul 31, 2012·Neurochemistry International·Guangfeng LiMartina Zimmermann
Sep 15, 2006·Journal of Cellular Physiology·Zhihao WuPeter A Campochiaro
Aug 21, 2007·Anti-cancer Drugs·Daniel NowakKai Uwe Chow
Nov 17, 2009·Drugs·Tadeusz RobakPawel Robak
Jan 24, 2006·Anti-cancer Drugs·Ting ChenChristopher C Taylor
Jun 15, 2007·The Journal of Biological Chemistry·Zhihao WuPeter A Campochiaro
Jan 4, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Adriano SpreaficoAnnalisa Santucci
Mar 29, 2020·Blood·Eun Ji GangYong-Mi Kim