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Molecular and Cellular Biology, March 2004, p. 2263-2276, Vol. 24, No. 6
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.6.2263-2276.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Agnes Csiszar, Elisabeth Vogelsang, and Maria Leptin*
Institut für Genetik, Universität zu Köln, Weyertal 121, D-50931 Cologne, Germany
Received 3 October 2003/ Accepted 11 December 2003
Signal transduction by fibroblast growth factor (FGF) receptors in Drosophila depends upon the intracellular protein Dof, which has been proposed to act downstream of the receptors and upstream of Ras. Dof is the product of a fast-evolving gene whose vertebrate homologs, BCAP and BANK, are involved in signaling downstream of the B-cell receptor. Mapping functional domains within Dof revealed that neither of its potential interaction motifs, the ankyrin repeats and the coiled coil, is essential for the function of Dof. However, we have identified a region within the N terminus of the protein with similarity to BCAP and BANK, which we refer to as the Dof, BCAP, and BANK (DBB) motif, that it is required for FGF-dependent signal transduction and is necessary for efficient interaction of Dof with the FGF receptor Heartless. In addition, we demonstrate that Dof is phosphorylated in the presence of an activated FGF receptor and that tyrosine residues could contribute to the function of the molecule.
Present address: School of Biological Sciences, University of WalesBangor, Bangor LL57 2UW, United Kingdom.
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