On behalf of Dr Lydia Tabernero. ### Applicants are invited to work on the *structure determination of regulatory complexes of MAP kinases*. Mitogen activated protein kinase (MAPK) pathways are at the crossroads of most cell signalling networks that transduce and integrate external stimuli like hormones, stress and environmental factors, into specific cellular responses. MAPK pathways are regulated by the specific association of protein kinases to efector proteins that control their subcellular location and activity. Alterations in the regulation of the pathway result in uncontrolled cell proliferation and tumour formation. Therefore, understanding the basis for the molecular recognition and specific association of MAP kinases with their effectors stands at the foundation for therapeutical development against cancer and other diseases. An essential step in the activation of transcription factors by MAP-kinases is the nuclear translocation of protein kinases like ERK2 in the last step of the signalling cascade. Translocation to the nucleus depends upon interaction of ERK2 with nucleopore components and is downregulated by the intervention of protein tyrosine phosphatases. The nature of these interactions remains highly unexplored because of the lack of structural data on complexes of MAPKs and their regulatory partners. This exciting project is part of on going studies on the regulation of signalling pathways involved in cell proliferation, angiogenesis and cancer in our laboratory. We use a multidisciplinary approach ranging from molecular biology and biochemistry to structural biology and bioinformatics to understand, at the molecular level, essential problems in protein-protein interactions, specific binding and how protein complexes assemble to transduce signals in the cell. Our laboratory is a member of the multidisciplinary *Marie Curie research training network (PTPNET)* recently funded by the EU-FP6 ( http://www.ich.ucl.ac.uk/ich/academicunits/PTPNET/Homepage) that offers the opportunity to interact with different European laboratories.
The Faculty of Life Sciences is a 5* rated department located in the new research institute (ICMCB-Michael Smith Building), funded by the Wellcome Trust. The institute provides the highest standards in research and core facilities to promote excellence in a multidisciplinary environment. The successful graduate training programme attracts dozens of new graduate students every year to the faculty. Funding for individual studentships is available from Research Councils through the Research and Graduate School at the School of Biological Sciences: http://www.ls.manchester.ac.uk/postgraduate Informal enquiries should be made to: Dr. Lydia Tabernero Michael Smith Building Faculty of Life Sciences University of Manchester Tel: 0161 275 7794 email: [EMAIL PROTECTED] www.ls.manchester.ac.uk/research/themes/structuralbiology/ www.ls.manchester.ac.uk/research/themes/geneexpression/ References: Pulido, R, et al., (1998) EMBO J. 17, 7337-7350. Tarrega C, Rios P, Cejudo-Marin R, Blanco-Aparicio C, van der Berk L, Schepens J, Hendriks W, Tabernero L, and Pulido R. (2005). J Biol Chem. 2005; 280(45): 37885-94. Nordle, AKL., Rios, P., Gaulton, A., Pulido, R., Attwood, TK., and Tabernero, L. (2007) Proteins, 69, 19-31. ### Kind regards. Leo ------------------------------------------------------------ Chavas Leonard, Ph.D. Research Associate ------------------------------------------------------------ Faculty of Life Sciences The University of Manchester The Michael Smith Building Oxford Road Manchester Lancashire M13 9PT ------------------------------------------------------------ Tel: +44(0)161-275-1586 e-mail: [EMAIL PROTECTED]
