Tau interacts with src-family non-receptor tyrosine kinases

Tau and other microtubule-associated proteins promote the assembly and stab ilization of neuronal microtubules. While each microtubule-associated prote in has distinct properties, their in vivo roles remain largely unknown. Tau is important in neurite outgrowth and axonal development. Recently, we sho wed that the amino-terminal region of tau, which is not involved in microtu bule interactions, is important in NGF induced neurite outgrowth in PC12 ce lls, Here we report that a proline rich sequence in the amino terminus of t au interacts with the SH3 domains of fyn and src non-receptor tyrosine kina ses, Tau and fyn were coimmunoprecipitated from human neuroblastoma cells a nd co-localization of tau and fyn was visualized in cotransfected NIH3T3 ce lls. Co-transfection of tau and fyn also resulted in an alteration in NIH3T 3 cell morphology, consistent with an in vivo interaction. Fyn-dependent ty rosine phosphorylation of tau occurred in transfected cells and tyrosine ph osphorylated tau was identified in human neuroblastoma cells as well, Our d ata suggest that tau is involved in signal transduction pathways. An intera ction between tan and fyn may serve as a mechanism by which extracellular s ignals influence the spatial distribution of microtubules. The tyrosine pho sphorylation of tau by fyn may also have a role in neuropathogenesis, as fy n is upregulated in Alzheimer's disease.