1. Signal transduction & gene regulation
Ligand binding induces dimerization and conformational changes in receptor-tyrosine kinases, resulting in the activation of the cytoplasmic tyrosine kinase domain. Multiple tyrosines of the receptor become phosphorylated and act as docking sites for signaling proteins that contain phospho-tyrosine binding domains called "SH2". These proteins activate signaling cascades that regulate cell shape, motility and proliferation. These effects are mediated in part by changing of expression of hundreds of genes.
Signal transduction by PDGF receptors
We used microarrays to monitor gene regulation by PDGF and FGF in fibroblasts, neurons and tumor cells. We are now working on transcription factors, such as SREBP, FOXO and STAT, which are activated by growth factors. We have developed bioinformatics tools named TFactS to predict the regulation of transcription factors in microarray data mining (Essaghir et al, 2010). We are developing other tools for functional gene expression data analysis.
Publications and supplementary material:
Essaghir A, Toffalini F, Knoops L, Kallin A, van Helden J, Demoulin JB.
Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data (TFactS).
Nucleic Acids Res. (2010) 38:e120.
Essaghir A, Dif N, Marbehant CY, Coffer PJ, Demoulin JB.
The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors.
J Biol Chem (2009)
284:10334-42.
Microarray data: GEO #GSE14256
Kallin A, Johannessen LE, Cani PD, Marbehant CY, Essaghir A, Foufelle F, Ferre P, Heldin CH, Delzenne NM, Demoulin JB.
SREBP1 regulates the expression of heme oxygenase 1 and the phosphatidylinositol-3 kinase regulatory subunit p55g.
J Lipid Res. (2007), 48:1628-36.
Microarray data: GEO #GSE6877 - ArrayExpress #E-TABM-215 - Supplementary material
Demoulin JB, Enarsson M, Larsson J, Essaghir A, Heldin CH and Forsberg-Nilsson K.
The gene expression profile of PDGF-treated neural stem cells corresponds to partially differentiated neurons and glia.
Growth Factors (2006), 24:184-96.
Microarray data: GEO #GSE3251 - ArrayExpress #E-TABM-39 - Supplementary material
Demoulin JB, Ericsson J, Kallin A, Rorsman C, Ronnstrand L, Heldin CH.
Platelet-derived growth factor stimulates membrane lipid synthesis through activation of phosphatidylinositol 3-kinase and sterol regulatory element-binding proteins.
J Biol Chem. (2004), 279:35392-402.
Microarray data: GEO #GSE1484 - ArrayExpress #E-MEXP-126 - Supplementary material
To know more... (pdf chapter of the last de Duve Institute report)
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