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Research > Research areas > Kinase Function in Brain

Kinase Function in Brain

Group leader

Eleanor Coffey, Ph.D.
Academy Research Fellow, Vice Director
eleanor.coffey [at] btk.fi

Contact information

Turku Centre for Biotechnology
P.O. Box 123, BioCity
(Street adr. Tykistökatu 6 B)
FIN-20521 Turku, Finland
+358-2-333 8605 (Eleanor Coffey)
+358-2-333 8000 (Fax Attn. Eleanor Coffey)
GSM: 348605

Description of the research

: Freshly isolated hippocampal neurons stained for MAP2 (yellow) and DNA (blue).

Neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease are characterised by the irreversible loss of nerve cell function. The protein kinases c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3 (GSK-3) are recognised as players in a broad range of diseases including stroke and neurodegenerative disease. However exactly how these proteins mediate neuronal death in the brain remains largely unknown. While targeting of protein kinases for drug-based therapy is already underway, our understanding of the physiological functions of these molecules in the brain is in its infancy. Our lab established a proteomics screen for identification of protein kinase substrates in the brain. Using this screen we have uncovered several novel protein kinase targets. The identification of targets combined with biochemical, genetic and imaging approaches have revealed unexpected functions for JNK in neocortex development and provided mechanistic insight to JNK action in neuronal disease.

Group members

Artur Padzik, Justyna Zdrojewska, Emilia Komulainen, Raghavendra Mysore, Prasannakumar Deshpande, Hasan Mohammed, Dani Flinkman, Jana Orellana Miguez, Patrik Hollos, Ravi Adusumalli. Individual information on group members can be found here Group members.

Alumni

Benny Björkblom, Hanna Heikelä, Vesa Hongisto, Wenrui Li, Elli Oksanen, Lihua Sun, Jenni Vainio, Nina Westerlund, Yubao Wang, Agniezka Bialek, Gunilla Hognas, Johanna Holmbom, Marit Jorgensen, Miikka Hurme, Julie Millour, Lenaig Marchand, Kimmo Mäkela, Iiris Nykanen, Annika Nymark, Annika Pienimaki, Emmy Rannikko, Maria Shariatmadari, Henna Sihvonen, Annika Smeds, Nina Smeds, Jenny Södermann, Rognoy Vibeke, Mats Österholm.

: Left to right: Raghavendra Mysore, Dani Flinkman, Artur Padzik, Eleanor Coffey, Justyna Zdrojewska, Emilia Komulainen, Hasan Mohammed, Prasannakumar Deshpande.

Funding

The Academy of Finland, Biocenter Finland, the Sigrid Juselius Foundation, Åbo Akademi University, Sitra, CIMO, TUBS graduate school, FP6 STREP and ToK.

Recent Publications

Mai, A., Veltel, S., Pellinen, T., Padzik, A., Coffey, E., Marjomäki, V., Ivaska, J. Competetive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. Journal of Cell Biology. 194(2), 291-306, 2011.

Westerlund N, Zdrojewska J, Padzik A, Komulainen E, Björkblom B, Rannikko E, Tararuk T, Garcia-Frigola C, Sandholm J, Nguyen L, Kallunki T, Courtney MJ, Coffey ET. Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate. Nature Neuroscience. 14, (3), 305-13, 2011

Matlawska-Wasowska K, Finn R, Mustel A, O'Byrne CP, Baird AW, Coffey ET, Boyd A. The vibrio parahaemolyticus Type III secretion systems manipulate host cell MAPK for critical steps in pathogenesis. BMC Microbiology. Dec 30th, 2010

Microtubule stabilization by BMP receptor-mediated scaffolding of JNK promotes dendrite formation. Podkowa M, Zhao X, Chow CW, Coffey ET, Davis RJ, Attisano L. Molecular and Cellular Biology. 2010

Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. (2009) Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Björkblom B, Coffey ET, Bagnato C, Han D, Huang CF, Banker G, Pigino G, Brady ST. Nature Neuroscience. 12(7):864-71.

Waetzig, V, Wacker, U, Haeusgen, Björkblom,B, Courtney, M.J., Coffey, E.T. Herdegen, T. (2009) Concurrent protective and destructive signalling of JNK2 in neuroblastoma cells. Cellular Signalling. 873-880.

Naumanen, T., Johansen, L.D., Coffey, E.T., Kallunki, T. (2008) Loss of function of IKAP/ELP1: Could neuronal migration defect underlie familial disautonomia? Cell Adhesion and Migration. Vol.2, Issue 4.

Benny Björkblom, Jenni C. Vainio, Vesa Hongisto, Thomas Herdegen, Michael Courtney, Eleanor Coffey. (2008) All JNKs can kill but nuclear localization is critical for neuronal death. Journal of Biological Chemistry. 283(28)19704-13.

Hongisto, V., Vainio, J.C., Thompson, R., Courtney, M.J., Coffey, E.T. (2008) The Wnt pool of GSK-3-beta is critical for trophic deprivation induced neuronal death. Molecular and Cellular Biology 28(5)1515-27. PDF

Dan Johansen, L., Naumanen, T., Knudsen, A., Westerlund, N., Gromova, I., Junttila, M., Nielsen, C., Bottzauw, T., Tolkovsky, A., Westermarck, J., Coffey, E.T., Jäättelä, M., Kallunki, T. (2008) IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration. Journal of Cell Science 121(6) 854-64.

Westerlund, N., Zdrojewska, J., Courtney, M.J., Coffey, E.T. (2008) SCG10 as a molecular effector of JNK1: Implications for the therapeutic targeting of JNK in nerve regeneration. Expert Opinion on Therapeutic Targets 12(1):31-43. PDF

Semenova, M.M., Mäki-Hokkonen, A.M.J., Cao, J., Komarovski, V., Forsberg, M., Koistinaho, M., Coffey, E.T., Courtney, M.J. (2007) Rho mediates calcium-dependent activation of p38alpha and subsequent excitotoxic cell death. Nature Neuroscience 10,(4):436-443

Tararuk, R., Östman, N., Li, W., Björkblom, B., Padzik, A., Zdrojewska, J., Hongisto, V., Herdegen, T., Konopka, W., Courtney, M.J., Coffey, E.T. (2006) JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length. Journal of Cell Biology 173(2):265-77

Björkblom, B., Östman, N., Hongisto, V., Komarovski, V., Filen, J., Nyman, T., Kallunki, T., Courtney, M., Coffey, E. (2005) Constitutively active cytoplasmic JNK1 is a dominant regulator of dendritic architecture; role of MAP2 as an effector. Journal of Neuroscience 25(27):6350-6361

Yang J, Lindahl M, Lindholm P, Virtanen H, Coffey E, Runeberg-Roos P, Saarma M. (2004) PSPN/GFRalpha4 has a significantly weaker capacity than GDNF/GFRalpha1 to recruit RET to rafts, but promotes neuronal survival and neurite outgrowth. FEBS Lett. 569:267-271

Cao J, Semenova MM, Solovyan VT, Han J, Coffey ET, Courtney MJ. (2004) Distinct requirements for p38alpha and c-Jun N-terminal kinase stress-activated protein kinase s in different forms of apoptotic neuronal death. Journal of Biological Chemistry 279:35903-35913

Hongisto V, Smeds N, Brecht S, Herdegen T, Courtney MJ, Coffey ET. (2003) Lithium blocks the c-Jun stress response and protects neurons via its action on glycogen synthase kinase 3. Molecular Cell Biology 23:6027-6036

Coffey E.T., Smiciene G., Hongisto V., Cao J., Brecht S., Herdegen T., Courtney M.J. (2002) c-Jun N-terminal protein kinase (JNK) 2/3 is specifically activated by stress, mediating c-Jun activation, in the presence of constitutive JNK1 activity in cerebellar neurons. Journal of Neuroscience 22:4335-4345

Hietakangas V, Elo I, Rosenstrom H, Coffey ET, Kyriakis JM, Eriksson JE, Sistonen L. (2001) Activation of the MKK4-JNK pathway during erythroid differentiation of K562 cells is inhibited by the heat shock factor 2-beta isoform. FEBS Lett. 505:168-172

Coffey, E.T., Hongisto, V., Dickens, M., Davis, R.J. and Courtney, M.J. (2000) Dual Roles for c-Jun N-terminal Kinase in Developmental and Stress Responses in Cerebellar granule Neurons. Journal of Neuroscience 20, 7602–7613

Courtney, M.J. and Coffey, E.T. (1999) The mechanisms of ARA-C induced apoptosis of differentiating cerebellar granule neurons. European Journal of Neuroscience. 11:1073-1084

Courtney, M.J., Åkerman, K.E.O. and Coffey, E.T. (1997) Neurotrophins protect cultured cerebellar granule cells against the early phase of cell death by a two-component mechanism. Journal of Neuroscience 17, 4201-4211

Coffey ET, Akerman KE, Courtney MJ. (1997) Brain derived neurotrophic factor induces a rapid upregulation of synaptophysin and tau proteins via the neurotrophin receptor TrkB in rat cerebellar granule cells. Neuroscience Letters. 227:177-180