MU-OPIOIDS ACTIVATE TYROSINE KINASE FOCAL ADHESION KINASE AND REGULATE CORTICAL CYTOSKELETON PROTEINS CORTACTIN AND VINCULIN IN CHICK EMBRYONIC NEURONS

We have investigated the signal transduction pathway of the G-protein mu-opioid receptor upstream of phospholipase D (PLD) and protein kinas e C-epsilon (PKC-epsilon) activation in postmitotic E6CH chick embryo cortical neurons, The mu-opioid receptor and PLD-PKC-epsilon functiona l coupling depends on upstream tyrosine kinase activation, We now repo rt that the mu-opioid agonists specifically stimulated tyrosine phosph orylation and activation of the focal adhesion kinase (FAK) in a time- dependent manner, We also demonstrate that met-enkephalin, a mu-opioid agonist in E6CH cultures, significantly increases tyrosine phosphoryl ation of another Src kinase substrate, the cytoskeletal protein cortac tin, Tyrosine phosphorylation of cortactin led to drastic changes in s ubcellular localization, an estimated 2-fold enrichment in the cytosol , Similarly, opioids stimulated a sustained tyrosine phosphorylation o f vinculin, a protein enriched in focal adhesion sites, These data pro vide novel evidence that opioid receptor intracellular signaling engag es the specific activation of tyrosine kinase FAK and regulates the ne uronal cytoskeleton during central nervous system morphogenesis. (C) 1 997 Wiley-Liss,Inc.