Protein kinase C and F-actin are essential for stimulation of neuronal FAK tyrosine phosphorylation by G-proteins and amyloid beta protein

Focal adhesion kinase (FAK) is a protein tyrosine kinase implicated in signal transduction pathways for integrins, neuropeptides, and lysophosphatidic acid, FAK, first discovered in non-neuronal cells, recently has been reported to occur in neurons, where its tyrosine phosphorylation is upregulated by fibronectin and by the Alzheimer's A beta peptide, The current work has elucidated molecular events leading to tyrosine phosphorylation of FAK in the rat B103 CNS nerve cell line, Activation of receptor-coupled G-proteins by Mas-7 was found to evoke rapid upregulation of FAK tyrosine phosphorylation (Tyr(P)), Upregulation by Mas-7 was blocked by GF109203X, a potent inhibitor of protein kinase C (PRC), Phorbol ester also upregulated FAK-YP, verifying a role for PKC in the transduction cascade, Upregulation of FAK-YP by activation of G-proteins and PKC was dependent upon intact F-actin, as cytochalasin D abolished stimulation by Mas-7 and by phorbol ester, The relatively slow increase in FAK-YP evoked by chronic exposure to A beta also was abolished by GF109203X and by cytochalasin D, The results show that tyrosine phosphorylation of FAK in neurons is regulated positively by PKC, functioning down-stream from G-proteins through an F-actin-dependent mechanism, The Alzheimer's A beta peptide is capable of activating elements of this same signal transduction pathway, via membrane events that remain to be determined.