Tau interacts with src-family non-receptor tyrosine kinases.
Tau and other microtubule-associated proteins promote the assembly and stabilization of neuronal microtubules. While each microtubule-associated protein has distinct properties, their in vivo roles remain largely unknown. Tau is important in neurite outgrowth and axonal development. Recently, we showed that the amino-terminal region of tau, which is not involved in microtubule interactions, is important in NGF induced neurite outgrowth in PC12 cells. Here we report that a proline rich sequence in the amino terminus of tau interacts with the SH3 domains of fyn and src non-receptor tyrosine kinases. Tau and fyn were co-immunoprecipitated from human neuroblastoma cells and co-localization of tau and fyn was visualized in co-transfected NIH3T3 cells. Co-transfection of tau and fyn also resulted in an alteration in NIH3T3 cell morphology, consistent with an in vivo interaction. Fyn-dependent tyrosine phosphorylation of tau occurred in transfected cells and tyrosine phosphorylated tau was identified in human neuroblastoma cells as well. Our data suggest that tau is involved in signal transduction pathways. An interaction between tau and fyn may serve as a mechanism by which extracellular signals influence the spatial distribution of microtubules. The tyrosine phosphorylation of tau by fyn may also have a role in neuropathogenesis, as fyn is upregulated in Alzheimer's disease.
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. gloria-lee@uiowa.edu
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D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009447:Neuroblastoma / Q000473:pathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016875:tau Proteins; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases