A novel cross-talk in signal transduction

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Project objective

Growth factors of the neuropeptide family ( bombesin, vasopressin, endothelin, bradykinin) stimulate DNA syntesis and proliferation in cultured cells and are implicated as growth factors in a variety of biological processes, including development, tissue regeneration and tumorigenesis. Recently, bombesin and other neuropeptides have been shown to stimulate a rapid increase in tyrosine phosphorylation of multiple substrates in 3T3 cells. Two of these proteins could be identified as p125FAK, a novel cytosolic tyrosine kinase with no typical SH2 and SH3 domains and paxillin, a cytoskeletal associated protein. We plan to examine potential interactions between the SH2 domains of a variety of signalling and adaptor proteins with proteins which are tyrosine phosphorylated in response to neuropeptides. In particular, it is planned to define whether p125FAK and paxillin can form complexes with the SH2- domains of other signalling molecules ( p85alpha, Src, Crk, pl30CaS,Grb-2, Shc, Sos ) and whether paxillin is associated with p125FAK as a constitutive complex or if the complex is formed in response to ligands that stimulate tyrosine phosphorylation. This could clarify the signalling network involving cytoskeletal rearrangments, mitogenic phathways and cellular transformation.

Original text from CORDIS.

Participants

• Imperial Cancer Research Fund · LondonCoordinatorUnited Kingdom
• Not availableCity levelItaly

Links

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