|
|
|
Effect of inhibiting tyrosine kinase Src expression
on protein phosphatase 2A and tau phosphorylation |
| LIU Rong1, ZENG Ji2, ZHOU Xinwen3, WANG Jianzhi3, PEI Jinjing4 |
| 1.Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology; Karolinska Institutet, KI-Alzheimer Disease Research Center (KI-ADRC); 2.Clinical Laboratory of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 3.Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology; 4.Karolinska Institutet, KI-Alzheimer Disease Research Center (KI-ADRC); |
|
|
|
|
Abstract 1The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphorylation, protein phosphatase 2A (PP2A) activity, and on tau phosphorylation. Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein, and the phosphorylation levels of PP2A Y307 and tau at different sites, as well as PP2A activity were detected at different time points after siRNA transfection. Twelve hours after siRNA transfection, the protein level of Src was dramatically decreased, with decreased PP2A Y307 phosphorylation. However, the total PP2A protein level was also decreased, together with a decreased PP2A activity. Tau was hyperphosphorylated at the Ser198/199/202 sites. Multiple factors may be involved in the cellular regulation of PP2A activity. Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.
|
|
Issue Date: 05 September 2008
|
|
| 1 |
Arriagada P V, Growdon J H, Hedley-Whyte E T, Hyman B T . Neurofibrillarytangles but not senile plaques parallel duration and severity of Alzheimer'sdisease. Neurology, 1992, 42(3): 631–639
|
| 2 |
Grundke-Iqbal I, Iqbal K, Tung Y C, Quinlan M, Wisniewski H M, Binder L I . Abnormal phosphorylation of the microtubule-associatedprotein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA, 1986, 83(13): 4913–4917.
doi:10.1073/pnas.83.13.4913
|
| 3 |
Janssens V, Goris J . Protein phosphatase 2A: ahighly regulated family of serine/threonine phosphatases implicatedin cell growth and signalling. BiochemJ, 2001, 353(Pt 3): 417–439.
doi:10.1042/0264‐6021:3530417
|
| 4 |
Liu F, Grundke-Iqbal I, Iqbal K, Gong C X . Contributionsof protein phosphatases PP1, PP2A, PP2B and PP5 to the regulationof tau phosphorylation. Eur J Neurosci, 2005, 22(8): 1942–1950.
doi:10.1111/j.1460‐9568.2005.04391.x
|
| 5 |
Gong C X, Singh T J, Grundke-Iqbal I, Iqbal K . Phosphoproteinphosphatase activities in Alzheimer disease brain. J Neurochem, 1993, 61(3):921–927.
doi:10.1111/j.1471‐4159.1993.tb03603.x
|
| 6 |
Liu F, Liang Z, Gong C X . Hyperphosphorylation of tau and protein phosphatasesin Alzheimer disease. Panminerva Med, 2006, 48(2): 97–108
|
| 7 |
Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White C L 3rd : Downregulationof protein phosphatase 2A carboxyl methylation and methyltransferasemay contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol, 2004, 63(10): 1080–1091
|
| 8 |
Chen J, Martin B L, Brautigan D L . Regulation of protein serine-threonine phosphatase type-2Aby tyrosine phosphorylation. Science, 1992, 257(5074): 1261–1264.
doi:10.1126/science.1325671
|
| 9 |
Pei J J, Gong C X, Iqbal K, Grundke-Iqbal I, Wu Q L, Winblad B, Cowburn R F . Subcellular distribution of protein phosphatases and abnormally phosphorylatedtau in the temporal cortex from Alzheimer's disease and control brains. J Neural Transm, 1998, 105(1): 69–83.
doi:10.1007/s007020050039
|
| 10 |
Garcia A, Cayla X, Guergnon J, Dessauge F, Hospital V, Rebollo MP, Fleischer A, Rebollo A . Serine/threonine proteinphosphatases PP1 and PP2A are key players in apoptosis. Biochimie, 2003, 85(8): 721–726.
doi:10.1016/j.biochi.2003.09.004
|
| 11 |
Gong C X, Lidsky T, Wegiel J, Zuck L, Grundke-Iqbal I, Iqbal K .Phosphorylation of microtubule-associated protein tauis regulated by protein phosphatase 2A in mammalian brain. Implicationsfor neurofibrillary degeneration in Alzheimer's disease. J Biol Chem, 2000, 275(8): 5535–5544.
doi:10.1074/jbc.275.8.5535
|
| 12 |
Sontag E, Nunbhakdi-Craig V, Lee G, Bloom G S, Mumby M C . Regulation of the phosphorylation stateand microtubule-binding activity of Tau by protein phosphatase 2A. Neuron, 1996, 17(6): 1201–1207.
doi:10.1016/S0896‐6273(00)80250‐0
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
