Literature: A-K ; L-Z ; subject area
Compiled by: Julian Thorpe
Mitogen-Activated Protein Kinase (MAP kinase)
|
Please Note: Due to time constraints, the text part of this page has not been updated for some time. However, references are added reasonably frequently. |
MAP kinases (mitogen-activated protein kinase; externally regulated kinase, [ERK1 and ERK2]) are a sub-family of the protein kinases (e.g. see Cobb et al., 1995).
 | MAP kinases are so termed because they are activated by mitogens
and therefore potentially signal entry into the cell cycle. The MAP kinase
pathway is one branch of the complex cellular regulatory machinery, the aberrant
activation of which may contribute to the hyperphosphorylation of
tau
associated with AD. MAP kinases (Cobb et al., 1995) are serine-threonine
kinases that have a significant role in hormonal signal transduction.
They are activated by MAP kinase kinase (MAP kinase/ERK kinase: MEK).
MEKs are highly specific for ERK1 and 2. MEKs are themselves activated
by MEK kinase. The latter and MAP kinases are highly-expressed in the
brain, with ERK1 mRNA apparently enriched in astrocytes and glia. ERK2 has
been found in neuronal processes, tangles
and plaques
(Trojanowski et al., 1993). |
| ERK1 is a 43kDa and ERK2 a 41kDa protein (they have c. 83% homology).
They have a specificity (shared with cyclin-dependent kinase 2) for substrates
with phosphorylated serine or threonine residues preceding a proline
(they are thus serine-threonine kinases). The phosphorylation of both
a tyrosine and a threonine (that lie one amino acid apart on each of
the two enzymes) are required for activation of the highest MAP kinase
activity. MAP kinases are regulated by autocrine and paracrine growth
factors (e.g. nerve growth factor [NGF] and ciliary neurotrophic factor [CNTF]). These latter stimulate neuronal proliferation, development and
differentiation. |
| The MAP kinases phosphorylate many key regulatory proteins such as other protein kinases, transcription factors (thereby act in the nucleus to alter gene expression; e.g. Egr1; Harada et al., 2001), membrane enzymes and cytoskeletal proteins (including tau ; Ferrer et al., 2001). It has also now been demonstrated (in PC12 cells; Harada et al., 2001) that activation of the MAP kinase pathway by nerve growth factor induces p35, the neuron-specific activator of Cdk5 . This induction is mediated via the transcription factor Egr1. Significantly, MAP kinases can phosphorylate tau in up to 15 of the 17 Ser-Pro or Thr-Pro motifs of the largest human isoform and have been seen to be associated with complexes of tau (and neurofilament and tubulin proteins; Veeranna et al., 2000). A secreted fragment of the amyloid protein precursor (APP) can stimulate MAP kinase in a ras-dependent manner, leading to tau phosphorylation (Kosik et al., 1995). The results suggested an interaction of tau with actin in addition to microtubules . On this note, it has been suggested (Yuan and Yankner, 2000 ) that, in AD, amyloid fibrils may activate cell death signalling pathways involving the neurotrophins which regulate apoptosis via protein kinase cascades (inc. the MAP kinase pathway). |
| Inactivation of MAP kinases: see Phosphatases . |
 | Often initiated by activation of a tyrosine kinase receptor (e.g. EGF or PDGF) |
| This receptor activates the Ras pathway (via an adaptor protein) |
| The latter leads to activation of the Raf Ser/Thr kinase |
| Raf Ser/Thr kinase then activates MAP kinase kinase (or MEK) |
| As the name suggests, the latter phosphorylates a MAP kinase and the pathway leading from MEK through phosphorylation of a MAP kinase which in turn phosphorylates another such enzyme, etc.. is sometimes called the MAP kinase pathway. |
| The latter leads ultimately to the phosphorylation of transcription factors (triggering changes in cell growth or differentiation) or of cytoskeletal proteins . |
Abe, K and Saito, H (2000) Amyloid beta neurotoxicity not mediated by the mitogen-activated protein kinase cascade in cultured rat hippocampal and cortical neurons. NEUROSCIENCE LETTERS 292: 1-4
Ahlijanian MK; Barrezueta NX; Williams RD; Jakowski A; Kowsz KP; McCarthy S; Coskran T; Carlo A; Seymour PA; Burkhardt JE;Nelson RB; McNeish JD (2000). Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Proc Natl Acad Sci USA 97: 2910-2915
Atzori, C, Ghetti, B, Piva, R, Srinivasan, AN, Zolo, P, Delisle, MB, Mirra, SS, Migheli, A (2001) Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY 60: 1190-1197
Bennecib, M, Gong, CX, Wegiel, J, Lee, MH, Grundke-Iqbal, I and Iqbal, K (2000) Inhibition of protein phosphatases and regulation of tau phosphorylation in rat brain. ALZHEIMERS REPORTS 3: 295-304
Bogoyevitch, MA, Boehm, I, Oakley, A, Ketteman, AJ, Barr, RK (2004) Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 1697: 89-101
Brownlees J, Yates A, Bajaj NP, Davis D, Anderton BH, Leigh PN, Shaw CE, Miller CC (2000) Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3. J Cell Sci 113: 401-7
Bruce-Keller, AJ, Keeling, JL, Keller, JN, Huang, FF, Camondola, S and Mattson, MP (2000) Antiinflammatory effects of estrogen on microglial activation. ENDOCRINOLOGY 141:3646-3656
Bulavin, DV, Fornace, AJ (2004) p38 MAP kinase's emerging role as a tumor suppressor. ADVANCES IN CANCER RESEARCH 92: 95-118
BUSH_ML, MIYASHIRO_JS, INGRAM_VM. (1995) ACTIVATION OF A NEUROFILAMENT KINASE, A TAU KINASE, AND A TAU PHOSPHATASE BY DECREASED ATP LEVELS IN NERVE GROWTH FACTOR-DIFFERENTIATED PC-12 CELLS. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, Vol.92, No.6, pp.1861-1865
Cobb, M.H., Hepler, J.E., Zhen, E., Ebert, D., Cheng, M., Dang, A. and Robbins, D. (1995) Regulation and Structure of the MAP Kinases ERK1 and ERK2. pp. 78-87 In: Alzheimer's Disease: Lessons from Cell Biology. Eds. K.S. Kosik, Y. Christen and D.J. Selkoe. Springer-Verlag.
Crenshaw DG, Yang J, Means AR, Kornbluth S (1998) The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1. EMBO J 17:1315-1327
Dineley, KT, Westerman, M, Bui, D, Bell, K, Ashe, KH and Sweatt, JD (2001) beta-amyloid activates the mitogen-activated protein kinase cascade via hippocampal alpha 7 nicotinic acetylcholine receptors: In vitro and in vivo mechanisms related to Alzheimer's disease. JOURNAL OF NEUROSCIENCE 21: 4125-4133
Echeverria, V, Ducatenzeiler, A, Dowd, E, Janne, E, Grant, SM, Szyf, M, Wandosell, F, Avila, J, Grimm, H, Dunnett, SB, Hartmann, T, Alhonen, L, Cuello, AC (2004) Altered mitogen-activated protein kinase signaling, tau hyperphosphorylation and mild spatial learning dysfunction in transgenic rats expressing the beta-amyloid peptide intracellularly in hippocampal and cortical neurons. NEUROSCIENCE 129: 583-592
Ekinci, FJ, Ortiz, D, Shea, TB (2003)
Okadaic acid mediates tau phosphorylation via sustained activation of the
L-voltage- sensitive calcium channel. MOLECULAR BRAIN RESEARCH 117: 145-151
Ferrer, I (2004) Stress kinases involved in tau phosphorylation in Alzheimer's disease, tauopathies and APP transgenic mice. NEUROTOXICITY RESEARCH 6: 469-475
Ferrer, I, Blanco, R, Carmona, M, Puig, B (2001) Phosphorylated mitogen-activated protein kinase (MAPK/ERK-P), protein kinase of 38kDa (p38-P), stress-activated protein kinase (SAPK/JNK-P), and calcium/calmodulin-dependent kinase II (CaM kinase II) are differentially expressed in tau deposits in neurons and glial cells in tauopathies. JOURNAL OF NEURAL TRANSMISSION 108: 1397-1415
Ferrer, I, Blanco, R, Carmona, M, Puig, B, Barrachina, M, Gomez, C, Ambrosio, S (2001) Active, phosphorylation-dependent mitogen-activated protein kinase (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 kinase expression in Parkinson's disease and Dementia with Lewy bodies. JOURNAL OF NEURAL TRANSMISSION 108: 1383-1396
Ferrer, I, Blanco, R, Carmona, M, Ribera, R, Goutan, E, Puig, B, Rey, MJ, Cardozo, A, Vinals, F and Ribalta, T (2001) Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau deposition in neurones and glial cells, but not with increased nuclear DNA vulnerability and cell death, in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. BRAIN PATHOLOGY 11: 144-158
Frasca, G, Chiechio, S, Vancher, C, Nicoletti, F, Copani, A, Sortino, MA (2004) beta-amyloid-activated cell cycle in SH-SY5Y neuroblastoma cells - Correlation with the MAP kinase pathway. JOURNAL OF MOLECULAR NEUROSCIENCE 22: 231-235
Garcia, ML and Cleveland, DV (2001) Going new places using an old MAP: tau, microtubules and human neurodegenerative disease. CURRENT OPINION IN CELL BIOLOGY 13: 41-48
Gasparini, L, Gouras, GK, Wang, R, Gross, RS, Beal, MF, Greengard, P and Xu, HX (2001) Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. JOURNAL OF NEUROSCIENCE 21: 2561-2570
Giasson_BI, Mushynski_WE. (1997) Study of proline-directed protein kinases involved in phosphorylation of the heavy neurofilament subunit. JOURNAL OF NEUROSCIENCE, 1997, Vol.17, No.24, pp.9466-9472
Gong C-X, Lidsky T, Weigel J, Zuck L, Grundke-Iqbal, I, Iqbal K (2000) Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. J Biol Chem 275: 5535-5544
Goodenough, S, Engert, S and Behl, C (2000) Testosterone stimulates rapid secretory amyloid precursor protein release from rat hypothalamic cells via the activation of the mitogen-activated protein kinase pathway. NEUROSCIENCE LETTERS 296: 49-52
Harada, T., Morooka, T., Ogawa, S. and Nishida, E. (2001) ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1 . Nature Cell Biology 3: 453 - 459
Harper, SJ, Wilkie, N (2003) MAPKs:
new targets for neurodegeneration. EXPERT OPINION ON THERAPEUTIC TARGETS 7:
187-200
Harris, FM, Brecht, WJ, Xu, Q, Mahley, RW, Huang, YD (2004) Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase - Modulation by zinc. JOURNAL OF BIOLOGICAL CHEMISTRY 279: 44795-44801
Holzer, M, Rodel, L, Seeger, G, Gartner, U, Narz, F, Janke, C, Heumann, R, Arendt, T (2001) Activation of mitogen-activated protein kinase cascade and phosphorylation of cytoskeletal proteins after neurone-specific activation of p21ras. II. Cytoskeletal proteins and dendritic morphology. NEUROSCIENCE 105: 1041-1054
HOSOI_T, UCHIYAMA_M, OKUMURA_E, SAITO_T, ISHIGURO_K, UCHIDA_T, OKUYAMA_A, KISHIMOTO_T, HISANAGA_S. (1995) EVIDENCE FOR CDK5 AS A MAJOR ACTIVITY PHOSPHORYLATING TAU-PROTEIN IN PORCINE BRAIN EXTRACT. JOURNAL OF BIOCHEMISTRY, 1995, Vol.117, No.4, pp.741-749
Hsu T, McRackan D, Vincent TS and H. Gert de Couet (2001) Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. Nature Cell Biology 3: 538 - 543
Hugon, J., Sindou, P., Lesort, M., Couratier, P., Esclaire, F. and Yardin, C. (1995) Modifications of phosphorylated tau immunoreactivity linked to excitotoxicity in neuronal cultures. pp. 172-179 In: Alzheimer's Disease: Lessons from Cell Biology. Eds. K.S. Kosik, Y. Christen and D.J. Selkoe. Springer-Verlag.
James_ND, Davis_DR, Sindon_J, Hanger_DP, Brion_JP, Miller_CCJ, Rosenberg_MP, Anderton_BH, Propst_F. (1996) Neurodegenerative changes including altered tau phosphorylation and neurofilament immunoreactivity in mice transgenic for the serine threonine kinase Mos. NEUROBIOLOGY OF AGING, 1996, Vol.17, No.2, pp.235-241
Johnson, GVW, Stoothoff, WH (2004) Tau phosphorylation in neuronal cell function and dysfunction. JOURNAL OF CELL SCIENCE 117: 5721-5729
Julien JP; Mushynski WE. (1998) Neurofilaments in health and disease.Prog Nucleic Acid Res Mol Biol, 1998, 61:, 1-23
Kim, SH, Smith, CJ, Van Eldik, LJ (2004) Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 beta production. NEUROBIOLOGY OF AGING 25: 431-439
Kosik KS, Ferreira A, Knowles R, Leclerc N and Greenberg SM (1995) Linking amyloid precursor protein processing and tau-related pathology in Alzheimer's disease. pp. 230-240 In: Alzheimer's Disease: Lessons from Cell Biology. Eds. K.S. Kosik, Y. Christen and D.J. Selkoe. Springer-Verlag.
Kuperstein, F, Yavin, E (2002) ERK activation and nuclear translocation in amyloid-beta peptide- and iron-stressed neuronal cell cultures. EUROPEAN JOURNAL OF NEUROSCIENCE 16: 44-54
Lambourne, SL, Sellers, LA, Bush, TG, Choudhury, SK, Ernson, PC, Suh, YH, Wilkinson, LS (2005) Increased tau phosphorylation on mitogen-activated protein kinase consensus sites and cognitive decline in transgenic models for Alzheimer's disease and FTDP-17: Evidence for distinct molecular processes underlying tau abnormalities. MOLECULAR AND CELLULAR BIOLOGY 25: 278-293
LEW_J, WANG_JH. (1995) NEURONAL CDC2-LIKE KINASE. TRENDS IN BIOCHEMICAL SCIENCES, 1995, Vol.20, No.1, pp.33-37
LEW_J, QI_Z, HUANG_QQ, PAUDEL_H, MATSUURA_I, MATSUSHITA_M, ZHU_XJ, WANG_JH. (1995) STRUCTURE, FUNCTION, AND REGULATION OF NEURONAL CDC2-LIKE PROTEIN-KINASE. NEUROBIOLOGY OF AGING, 1995, Vol.16, No.3, pp.263-268
Li, YK, Liu, L, Barger, SW, Griffin, WST (2003)
Interleukin-1 mediates pathological effects of microglia on tau phosphorylation
and on synaptophysin synthesis in cortical
Lichtenberg-Kraag B, Mandelkow EM, Biernat J, Steiner B, Schroter C, Gustke N, Meyer HE, Mandelkow E. (1992) Phosphorylation-dependent epitopes of neurofilament antibodies on tau protein and relationship with Alzheimer tau. Proc Natl Acad Sci U S A, 1992 Jun, 89:12, 5384-8
Mandelkow, E-M, Biernat, J., Lichtenberg-Kraag, B., Drewes, G., Wille, H., Gustke, N., Baumann, K. and Mandelkow, E. (1995) Phosphorylation of tau and its relationship with Alzheimer paired helical filaments. pp. 103-120 In: Alzheimer's Disease: Lessons from Cell Biology. Eds. K.S. Kosik, Y. Christen and D.J. Selkoe. Springer-Verlag.
Monje, PV, Gutkind, S (2004) Regulation of the transcriptional activity of c-Fos by ERK: A novel role for the prolyl-isomerase Pin1. MOLECULAR BIOLOGY OF THE CELL 15: 2490
Mudher, A, Chapman, S, Richardson, J, Asuni, A, Gibb, G, Pollard, C, Killick, R, Iqbal, T, Raymond, L, Varndell, I, Sheppard, P, Makoff, A, Gower, E, Soden, PE, Lewis, P, Murphy, M, Golde, TE, Rupniak, HT, Anderton, BH and Lovestone, S (2001) Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase. JOURNAL OF NEUROSCIENCE 21: 4987-4995
Nakamura Y; Hashimoto R; Kashiwagi Y; Aimoto S; Fukusho E; Matsumoto N; Kudo T; Takeda M (2000) Major phosphorylation site (Ser55) of neurofilament L by cyclic AMP-dependent protein kinase in rat primary neuronal culture. J Neurochem 74: 949-59
Peel, AL, Sorscher, N, Kim, JY, Galvan, V, Chen, S, Bredesen, DE (2004) Tau phosphorylation in Alzheimer's disease – Potential involvement of an APP-MAP kinase complex. NEUROMOLECULAR MEDICINE 5: 205-218
Pei, JJ, Braak, H, An, WL, Winblad, B, Cowburn, RF, Iqbal, K, Grundke-Iqbal, I (2002) Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease. MOLECULAR BRAIN RESEARCH 109: 45-55
Perry_G, Roder_H, Nunomura_A, Takeda_A, Friedlich_AL, Zhu_XW, Raina_AK, Holbrook_N, Siedlak_SL, Harris_PLR, Smith_MA. (1999) Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation. NEUROREPORT, 1999, Vol.10, No.11, pp.2411-2415
QI_Z, TANG_DM, MATSUURA_I, LEE_KY, ZHU_XJ, HUANG_QQ, WANG_JH. (1995) REGULATORY PROPERTIES OF NEURONAL CDC2-LIKE KINASE. MOLECULAR AND CELLULAR BIOCHEMISTRY, 1995, Vol.149, pp.35-39
Roder, H.M., Eden, P.A. and Ingram, V.M. (1993) Brain protein kinase pk40(erk) converts tau into a PHF-like form as found in Alzheimer's disease. Biochem. Biophys. Res. Comm. 193: 639-647
RODER_HM, HOFFMAN_FJ, SCHRODER_W. (1995) PHOSPHATASE RESISTANCE OF ERK2 BRAIN KINASE PK40(ERK2). JOURNAL OF NEUROCHEMISTRY, 1995, Vol.64, No.5, pp.2203-2212
Sahara, N, Vega, IE, Ishizawa, T, Lewis, J, McGowan, E, Hutton, M, Dickson, D, Yen, SH (2004) Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteins. JOURNAL OF NEUROCHEMISTRY 90: 829-838
Savage, MJ, Lin, YG, Ciallella, JR, Flood, DG, Scott, RW (2002) Activation of c-Jun N-terminal kinase and p38 in an Alzheimer's disease model is associated with amyloid deposition. JOURNAL OF NEUROSCIENCE 22: 3376-3385
Sengupta, A, Kabat, J, Novak, M, Wu, QL, Grundke-Iqbal, I and Iqbal, K (1998) Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubule. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 357: 299-309
Song, C, Perides, G, Wang, DC, Liu, YF (2002) beta-Amyloid peptide induces formation of actin stress
fibers through p38 mitogen-activated protein kinase
Sun, AY, Liu, M, Nguyen, XV, Bing, GY (2003)
p38 MAP kinase is activated at early stages in Alzheimer's disease brain.
EXPERIMENTAL NEUROLOGY 183: 394-405
Sun, J, Li, MT, Han, JH, Gu, J (2001) Sensitization of differentiated PC12 cells to apoptosis by presenilin-2 is mediated by p38. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 287: 536-541
Swatton, JE, Sellers, LA, Faull, RLM, Holland, A, Iritani, S, Bahn, S (2004) Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain. EUROPEAN JOURNAL OF NEUROSCIENCE 19: 2711-2719
Takeda K, Hatai T, Hamazaki TS, Nishitoh H, Saitoh M and Ichijo H (2000) Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells. J Biol Chem 275: 9805-9813
Tamagno, E, Robino, G, Obbili, A, Bardini, P, Aragno,
M, Parola, M, Danni, O (2003) H2O2 and 4-hydroxynonenal mediate amyloid
beta-induced neuronal apoptosis by activating JNKs and p38(MAPK). EXPERIMENTAL
NEUROLOGY 180: 144-155
Tokuoka H; Saito T; Yorifuji H; Wei F; Kishimoto T; Hisanaga S (2000) Brain-derived neurotrophic factor-induced phosphorylation of neurofilament-H subunit in primary cultures of embryo rat cortical neurons. J Cell Sci 113: 1059-68
Tomidokoro, Y, Ishiguro, K, Harigaya, Y, Matsubara, E, Ikeda, M, Park, JM, Yasutake, K, Kawarabayashi, T, Okamoto, K and Shoji, M (2001) A beta amyloidosis induces the initial stage of tau accumulation in APP(Sw) mice. NEUROSCIENCE LETTERS 299: 169-172
Trojanowski, J.Q., Mawal-Dewan, M., Scmidt, M.L., Martin, J. and Lee, VM-Y. (1993) Localisation of the mitogen activated protein kinase ERK2 in Alzheimer's Disease neurofibrillary tangles and senile plaque neurites. Brain Research 618: 333-337
Veeranna, Amin_ND, Ahn_NG, Jaffe_H, Winters_CA, Grant_P, Pant_HC. (1998) Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. JOURNAL OF NEUROSCIENCE, 1998, Vol.18, No.11, pp.4008-4021
Veeranna, Kaji, T, Boland, B, Odrljin, T, Mohan, P, Basavarajappa, BS, Peterhoff, C, Cataldo, A, Rudnicki, A, Amin, N, Li, BS, Pant, HC, Hungund, BL, Arancio, O, Nixon, RA (2004) Calpain mediates calcium-induced activation of the Erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons - Relevance to Alzheimer's disease. AMERICAN JOURNAL OF PATHOLOGY 165: 795-805
VEERANNA, SHETTY_KT, LINK_WT, JAFFE_H, WANG_J, PANT_HC. (1995) NEURONAL CYCLIN-DEPENDENT KINASE-5 PHOSPHORYLATION SITES IN NEUROFILAMENT PROTEIN (NF-H) ARE DEPHOSPHORYLATED BY PROTEIN PHOSPHATASE 2A. JOURNAL OF NEUROCHEMISTRY, 1995, Vol.64, No.6, pp.2681-2690
Veeranna GJ; Shetty KT; Takahashi M; Grant P; Pant HC (2000) Cdk5 and MAPK are associated with complexes of cytoskeletal proteins in rat brain. Brain Res Mol Brain Res, 2000 76: 229-36
Vincent, I, Rosado, M, Davies, P (1996) Mitotic mechanisms in Alzheimer's disease? JOURNAL OF CELL BIOLOGY 132: 413-425
Wells NJ, Watanabe N, Tokusumi T, Jiang W, Verdecia MA, Hunter A (1999) The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G2/M progression. J Cell Science 112: 3361-3371
Yang, SH, Sharrocks, AD, Whitmarsh, AJ (2003) Transcriptional regulation by the MAP kinase signaling cascades. GENE 320: 3-21
Yuan, JY and Yankner, BA (2000) Apoptosis in the nervous system. NATURE 407: 802-809
Zhao, WQ and Alkon, DL (2001) Role of insulin and insulin receptor in learning and memory. MOLECULAR AND CELLULAR ENDOCRINOLOGY 177: 125-134
Zhao, WQ, Feng, C, Alkon, DL (2003) Impairment of phosphatase 2A contributes to the prolonged MAP kinase phosphorylation in Alzheimer's disease fibroblasts. NEUROBIOLOGY OF DISEASE 14: 458-469
Zhu, XW, Castellani, RJ, Takeda, A, Nunomura, A, Atwood, CS, Perry, G, Smith, MA (2002) Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the 'two hit' hypothesis. MECHANISMS OF AGEING AND DEVELOPMENT 123: 39-46
Zhu, XW, Lee, HG, Raina, AK, Perry, G, Smith, MA (2002) The role of mitogen-activated protein kinase pathways in Alzheimer's disease. NEUROSIGNALS 11: 270-281
Zhu, XW, Rottkamp, CA, Hartzler, A, Sun, Z, Takeda, A, Boux, H, Shimohama, S, Perry, G, Smith, MA (2001) Activation of MKK6, an upstream activator of p38, in Alzheimer's disease. JOURNAL OF NEUROCHEMISTRY 79: 311-318
Zhu, XW, Sun, Z, Lee, HG, Siedlak, SL, Perry, G, Smith,
MA (2003) Distribution, levels, and activation of MEK1 in
Alzheimer's disease. JOURNAL OF NEUROCHEMISTRY 86: 136-142