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Relais et intégration des signaux intracellulaires

Intracellular signal relay and integration The development, plasticity and regenerative capabilities of the nervous system involves the proliferation of precursor cells, their differentiation, migration and the formation of their complex interconnexions. These various processes are under the control of extracellular cues inducing intracellular signaling pathways whose relay and integration is ensured in particular by phosphorylation-dephosphorylation of intracellular regulatory proteins. Within this general context, our group has identified several proteins and protein families which can be considered as likely supports for intracellular signaling pathways relay and integration, in particular in the nervous system. We presently focus our project on the phosphoproteins of the stathmin family, and on an original protein kinase, KIS, initially identified through its Stathmin family : Phosphoproteins of the stathmin family contribute to the control of the cytoskeleton through binding of tubulin.
We study the common and individual biological and molecular properties, roles and mechanisms of action of stathmin family proteins, including their specific partners and targets in the context of neuronal differentiation.
KIS : We aim to characterize roles and mechanisms of action of the protein kinase KIS in coupling RNA metabolism with cell signaling and hence brain physiology and behavior.
We combine the use of classical approaches such as the biochemical analysis of proteins, the biochemical and pharmacological analysis of signalling cascades in cell culture models including primary neuronal cells; the expression and silencing of proteins of interest in cell and/or organotypic cultures (transfection of recombinant and mutated cDNA, siRNA); the analysis of protein localisation and protein-protein interactions by dynamic cell imaging, confocal or electronic microscopy; the analysis of physiological consequences of functional perturbation of these proteins in transgenic mouse models.
- Ravelli,R.B.G., Gigant,B., Curmi,P.A., Jourdain,I., Lachkar,S., Sobel,A., and Knossow,M. (2004). Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. - Charbaut,E., Chauvin,S., Enslen,H., Zamaroczy,S., and Sobel,A. (2005). Two separate motifs cooperate to target stathmin-related proteins to the Golgi complex. - Gigant,B., Wang,C., Ravelli,R.B.G., Roussi,F., Steinmetz,M.O., Curmi,P.A., Sobel,A., and Knossow,M. (2005). Structural basis for the regulation of tubulin by vinblastine. - Manceau, V, Swenson, M, Le Caer, JP, Sobel, A, Kielkopf, CL, Maucuer, A (2006) Major phosphorylation of SF1 on adjacent Ser-Pro motifs enhances interaction with U2AF65. - Poulain, F.E., Sobel A. (2007) The "SCG10-LIke Protein" SCLIP is a novel regulator of axonal branching in hippocampal - Chauvin S., Poulain F.E., Ozon S. and. Sobel A (2008) Palmitoylation of stathmin family proteins domain A controls Golgi vs - Poulain F.E., Chauvin S., Wehrlé R., Desclaux M., Mallet J., Vodjdani G., Dusart I., Sobel A. (2008) SCLIP is crucial for the formation and development of the Purkinje cell dendritic arbor. - Manceau V., Kielkopf C.L., Sobel A. and Maucuer A. (2008) Different requirements of the kinase and UHM domains of KIS for its nuclear localisation and binding to splicing factors www.u839.idf.inserm.fr/page.asp?page=2044

Source: http://enpweb.3doublev.fr/enp/documents/equipes/equipeuk-17.pdf