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Louise Larose, Ph.D. Associate Professor, |
Research:
- Cellular signal transduction; Receptor Tyrosine Kinases, SH2 and SH3-containing adaptor proteins; Protein-Protein Interactions.
- Role of the adaptor protein Nck in mitogenesis, cell transformation and metabolism.
Signals through cell surface growth factor receptors commonly involve intrinsic tyrosine kinase activation, resulting in phosphorylation of the receptors and various cellular proteins. This creates high affinity binding sites for a variety of cytoplasmic proteins containing Src homology 2 (SH2) domains, which mediate further signal transduction events. Most of the SH2-containing proteins possess another distinct Src homology domain, the SH3. SH3 domains are also involved in protein interactions, but through recognition of proline rich sequences rather than tyrosine phosphorylated motifs in their target molecules. Among the SH2-, SH3-containing proteins, a special category referred to as adaptor proteins are defined by their lack of any particular catalytic activity. These adaptor proteins are believed to couple activated receptor tyrosine kinases (RTKs) with functional effector proteins via their SH2 and SH3 domains and thus promoting signal transduction. Nck, represented by two highly identical isoforms encoded by distinct genes, is an adaptor protein of 47kDa consisting of one SH2 and three SH3 domains. Nck associates with a variety RTKs and in fibroblasts, Nck overexpression induces cell transformation. Independently, of its role in mediating RTKs signaling, our laboratory has recently discovered that Nck directly modulates protein translation through its interaction with the ß-subunit of the eukaryotic initiation factor 2 (elF2ß). In summary, our research interests are to understand the role of adaptor proteins such Nck, by identifying and characterizing molecules interacting with these adaptors, and elucidating their functional significance in major cellular physiological and pathological processess.
Selected Publications:
Cardin*, E., and L. Larose. Modulation of PKR Nck interacts with PKR and inhibits its activation by dsRNA. BBRC 377:231-35, 2008. Supported by NSERC.
Cardin*, E., M. Latreille*, C. Khoury, M.T. Greenwood and L. Larose. Nck-1 selectively modulates eIF2aSer51 phosphorylation by a subset of eIF2a-kinases. FEBS J. 274:5865-75, 2007. Supported by NSERC.
Latreille, M*. and L. Larose. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2a signaling and cell survival to endoplasmic reticulum stress. J. Biol. Chem. 281(36): 26633-44, 2006. Supported by Canadian Diabetes Association
Jones, N., I.M. Blasutig, V. Eremina, J. Ruston, F. Bladt, H.Li, H. Huang, L. Larose, S.S.-C. Li, T. Tanako, S.E. Quaggin and T. Pawson. Nck adaptors link Nephrin to the actin cytoskeleton of kidneys podocytes. Nature 440:818-823, 2006.
Kebache*, S., E. Cardin, D. T. Nugent, E. Chevet and L. Larose. Nck-1 antagonizes Endoplasmic Reticulum stress-induced inhibition of translation. J. Biol. Chem. 279:9662-9671, 2004. Supported by CDA and NSERC.